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Sample records for overcome steric barriers

  1. Transforming Education: Overcoming Barriers.

    ERIC Educational Resources Information Center

    David, Jane L.; Goren, Paul D.

    Barriers to progress in educational reform exist inside and outside the education system. Some arise where new practices encounter traditional expectations and boundaries, but others go much deeper than education, such as poverty, racism, local political conflicts, and human resistance to change. The following five categories of barriers are…

  2. OVERCOMING CULTURAL BARRIERS.

    ERIC Educational Resources Information Center

    BARRUTIA, RICHARD

    THE RELATIONSHIP OF LANGUAGE DEVELOPMENT TO CULTURAL BARRIERS AND THE TEACHING OF FOREIGN LANGUAGES IS DISCUSSED IN THIS ARTICLE. VARIOUS VIEWS OF THE MEANING OF CULTURE ARE MENTIONED IN ORDER TO SINGLE OUT ANTHROPOLOGICAL CULTURE AS A MAIN FOCAL POINT. INTERCULTURAL DIFFERENCES ARE SPELLED OUT WITH EXAMPLES OF LINGUISTIC BARRIERS, AND…

  3. Overcoming Language Barriers

    PubMed Central

    De Buda, Yvonne

    1976-01-01

    Many family physicians in Canada experience language and cultural barriers between themselves and their patients. Several aspects of the ensuing problems are described and some practical suggestions for solutions are made. The importance of health education for new Canadians in the family physician's office as well as through the media and community projects is stressed. Imagesp68-ap68-bp70-a PMID:21308059

  4. Overcoming Barriers: Women in Superintendency

    ERIC Educational Resources Information Center

    Miller, Claire M.

    2009-01-01

    Women currently represent the largest number of teachers in the United States but remain underrepresented in the superintendent position. This suggests that the superintendency has been influenced by patriarchy. If women are to break through the barriers that prevent them from attaining a superintendency, we will need to understand the social…

  5. Overcome barriers to career success

    SciTech Connect

    Raudsepp, E.

    1983-04-01

    A test is given to determine if an engineer suffers from one of the three barriers to technical success: fear of success, fear of failure, or perfectionism. As in most such tests, the middle way is best. Successful engineers know that perfection cannot be attained, that they don't have time to worry about failure or success, and that by aiming and perservering in doing things well, success can be achieved.

  6. Overcoming Barriers in the Media Center

    ERIC Educational Resources Information Center

    Winter, Clint

    2011-01-01

    Web 2.0 has revolutionized one's ability to teach students in new and exciting ways. Students with disabilities can now overcome many barriers that once kept them from being successful in the regular education classroom. Media specialists can effectively advocate for students with disabilities. School library media specialists have the ability to…

  7. Overcoming Barriers to Engaging in College Academics

    ERIC Educational Resources Information Center

    Hensley, Lauren; Shaulskiy, Stephanie; Zircher, Andrew; Sanders, Megan

    2015-01-01

    Underprepared college students face transition issues that prevent full academic engagement. The written responses of 176 students in a learning-strategies course were used to develop a grounded model of overcoming barriers to academic engagement. Findings revealed contexts in which academic engagement involved high costs (i.e., effort, trade-off,…

  8. Overcoming Barriers to Palliative Care Consultation.

    PubMed

    Perrin, Kathleen Ouimet; Kazanowski, Mary

    2015-10-01

    Palliative care consultations for patients with life-threatening illnesses provide benefits for the patients and their families as well as for the health care team. Patients have better quality of life and live longer but cost the health care system less. Still, many patients are not offered the opportunity to receive a palliative care consultation. Barriers to palliative care consultation for patients in critical care units include misunderstandings about palliative care and not having agreed upon criteria for referral. Critical care nurses can assist in overcoming these barriers.

  9. Weather in Mountainous Terrain (Overcoming Scientific Barriers to Weather Support)

    DTIC Science & Technology

    2011-02-15

    Weather in Mountainous Terrain (Overcoming Scientific Barriers to Weather Support) Fiesta Resort & Conference Center Tempe, AZ February 1...Meteorology Overcoming Scientific Barriers to Weather Support Fiesta Resort & Conference Center Tempe, AZ February 1 & 2, 2010 Hosted by University

  10. Fortification: overcoming technical and practical barriers.

    PubMed

    Hurrell, Richard F

    2002-04-01

    The main barriers to successful iron fortification are the following: 1) finding an iron compound that is adequately absorbed but causes no sensory changes to the food vehicle; and 2) overcoming the inhibitory effect on iron absorption of dietary components such as phytic acid, phenolic compounds and calcium. These barriers have been successfully overcome with some food vehicles but not with others. Iron-fortified fish sauce, soy sauce, curry powder, sugar, dried milk, infant formula and cereal based complementary foods have been demonstrated to improve iron status in targeted populations. The reasons for this success include the use of soluble iron such as ferrous sulfate, the addition of ascorbic acid as an absorption enhancer or the use of NaFeEDTA to overcome the negative effect of phytic acid. In contrast, at the present time, it is not possible to guarantee a similar successful fortification of cereal flours or salt. There is considerable doubt that the elemental iron powders currently used to fortify cereal flours are adequately absorbed, and there is an urgent need to investigate their potential for improving iron status. Better absorbed alternative compounds for cereal fortification include encapsulated ferrous sulfate and NaFeEDTA, which, unlike ferrous sulfate, do not provoke fat oxidation of cereals during storage. Encapsulated compounds also offer a possibility to fortify low grade salt without causing off-colors or iodine loss. Finally, a new and useful additional approach to ensuring adequate iron absorption from cereal based complementary foods is the complete degradation of phytic acid with added phytases or by activating native cereal phytases.

  11. Overcoming a nucleosomal barrier to replication

    PubMed Central

    Chang, Han-Wen; Pandey, Manjula; Kulaeva, Olga I.; Patel, Smita S.; Studitsky, Vasily M.

    2016-01-01

    Efficient overcoming and accurate maintenance of chromatin structure and associated histone marks during DNA replication are essential for normal functioning of the daughter cells. However, the molecular mechanisms of replication through chromatin are unknown. We have studied traversal of uniquely positioned mononucleosomes by T7 replisome in vitro. Nucleosomes present a strong, sequence-dependent barrier for replication, with particularly strong pausing of DNA polymerase at the +(31–40) and +(41–65) regions of the nucleosomal DNA. The exonuclease activity of T7 DNA polymerase increases the overall rate of progression of the replisome through a nucleosome, likely by resolving nonproductive complexes. The presence of nucleosome-free DNA upstream of the replication fork facilitates the progression of DNA polymerase through the nucleosome. After replication, at least 50% of the nucleosomes assume an alternative conformation, maintaining their original positions on the DNA. Our data suggest a previously unpublished mechanism for nucleosome maintenance during replication, likely involving transient formation of an intranucleosomal DNA loop. PMID:27847876

  12. Fisher information and steric effect: study of the internal rotation barrier of ethane.

    PubMed

    Esquivel, Rodolfo O; Liu, Shubin; Angulo, Juan Carlos; Dehesa, Jesús S; Antolín, Juan; Molina-Espíritu, Moyocoyani

    2011-05-05

    On the basis of a density-based quantification of the steric effect [Liu, S. B. J. Chem. Phys.2007, 126, 244103], the origin of the internal rotation barrier between the eclipsed and staggered conformers of ethane is systematically investigated in this work from an information-theoretical point of view by using the Fisher information measure in conjugated spaces. Two kinds of computational approaches are considered in this work: adiabatic (with optimal structure) and vertical (with fixed geometry). The analyses are performed systematically by following, in each case, the conformeric path by changing the dihedral angle from 0 to 180° . This is calculated at the HF, MP2, B3LYP, and CCSD(T) levels of theory and with several basis sets. Selected descriptors of the densities are utilized to support the observations. Our results show that in the adiabatic case the eclipsed conformer possesses a larger steric repulsion than the staggered conformer, but in the vertical cases the staggered conformer retains a larger steric repulsion. Our results verify the plausibility for defining and computing the steric effect in the post-Hartree-Fock level of theory according to the scheme proposed by Liu.

  13. Overcoming Blocks and Barriers to Creativity.

    ERIC Educational Resources Information Center

    Raudsepp, Eugene

    1982-01-01

    Organizational barriers to creativity are examined. It is noted that resistance to change is a major impediment to creative problem solving in most organizations. Understanding the barriers to change that exist is viewed to help people exercise and develop their creativity more fully and effectively. (MP)

  14. Consumer and Employer Strategies for Overcoming Employment Barriers. Technical Report.

    ERIC Educational Resources Information Center

    Crudden, Adele; Williams, Wendy; McBroom, Lynn W.; Moore, J. Elton

    This report on strategies for overcoming employment barriers for persons with visual impairments summarizes comments and suggestions of 7 focus groups comprised of either consumers (n=49) or employers (n=19). The report first reviews the literature concerning employment barriers and how consumers in previous studies suggested these barriers be…

  15. Explaining and overcoming barriers to climate change adaptation

    NASA Astrophysics Data System (ADS)

    Eisenack, Klaus; Moser, Susanne C.; Hoffmann, Esther; Klein, Richard J. T.; Oberlack, Christoph; Pechan, Anna; Rotter, Maja; Termeer, Catrien J. A. M.

    2014-10-01

    The concept of barriers is increasingly used to describe the obstacles that hinder the planning and implementation of climate change adaptation. The growing literature on barriers to adaptation reveals not only commonly reported barriers, but also conflicting evidence, and few explanations of why barriers exist and change. There is thus a need for research that focuses on the interdependencies between barriers and considers the dynamic ways in which barriers develop and persist. Such research, which would be actor-centred and comparative, would help to explain barriers to adaptation and provide insights into how to overcome them.

  16. Overcoming cellular barriers for RNA therapeutics.

    PubMed

    Dowdy, Steven F

    2017-03-01

    RNA-based therapeutics, such as small-interfering (siRNAs), microRNAs (miRNAs), antisense oligonucleotides (ASOs), aptamers, synthetic mRNAs and CRISPR-Cas9, have great potential to target a large part of the currently undruggable genes and gene products and to generate entirely new therapeutic paradigms in disease, ranging from cancer to pandemic influenza to Alzheimer's disease. However, for these RNA modalities to reach their full potential, they first need to overcome a billion years of evolutionary defenses that have kept RNAs on the outside of cells from invading the inside of cells. Overcoming the lipid bilayer to deliver RNA into cells has remained the major problem to solve for widespread development of RNA therapeutics, but recent chemistry advances have begun to penetrate this evolutionary armor.

  17. Overcoming the English-language barrier

    NASA Astrophysics Data System (ADS)

    Mahoney, Terry J.

    Astronomers from non-English-speaking countries, who form a sizeable proportion of the astronomical research community, are obliged to communicate the results of their investigations in a language that is not their own. Consequently, good science is frequently masked by poor command of English, which can create an unnecessary barrier to the communication of scientific results. A suggested method of surmounting the language barrier is the setting up of scientific editorial services in at least the major astronomical centres. It is further argued that journal editors, rather than scientific referees, should be responsible for judging the linguistic and stylistic quality of articles presented for publication. The peer-review system would then be restricted exclusively to the scientific rather than linguistic content of papers presented. The scientific Editorial Service of the Instituto de Astrofisica de Canarias, in operation since 1996, is briefly described in this context.

  18. Desensitization: Overcoming the Immunologic Barriers to Transplantation

    PubMed Central

    Choi, Jua; Vo, Ashley; Peng, Alice; Jordan, Stanley C.

    2017-01-01

    HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection. PMID:28127571

  19. Overcoming Nonviral Gene Delivery Barriers: Perspective and Future

    PubMed Central

    Jones, Charles H.; Chen, Chih-Kaung; Ravikrishnan, Anitha; Rane, Snehal; Pfeifer, Blaine A.

    2013-01-01

    A key end goal of gene delivery research is to develop clinically-relevant vectors that can be used to combat elusive diseases such as AIDS. Despite promising engineering strategies, efficiency and ultimately gene modulation efficacy of nonviral vectors have been hindered by numerous in vitro and in vivo barriers that have resulted in sub-viral performance. In this perspective, we concentrate on the gene delivery barriers associated with the two most common classes of nonviral vectors, cationic-based lipids and polymers. We present the existing delivery barriers and summarize current vector-specific strategies to overcome said barriers. PMID:24093932

  20. Overcoming Barriers to School Based Research: A Local School Perspective.

    ERIC Educational Resources Information Center

    Epps, Jean M.

    The importance of collaboration between professional research and professional personnel in the classroom and school office is described, and suggestions are made for overcoming barriers to effective collaboration. Crandall's conditions for effective collaboration are: that the participants possess substantive competency; that both organizations…

  1. Overcoming barriers to Baby-Friendly status: one hospital's experience.

    PubMed

    McKeever, Joyce; Fleur, Rose St

    2012-08-01

    The journey toward Baby-Friendly status at Jersey Shore University Medical Center in Neptune, NJ began with a desire to improve overall breastfeeding rates at the hospital. Although evidence showed that hospitals that incorporated some or all of the Ten Steps to Successful Breastfeeding had improved breastfeeding rates, it was difficult to overcome barriers that prevented the hospital physicians and nursing staff from seeing the value in adopting this quality initiative. Long-standing practices combined with misinformation compounded the problem. That situation changed when several factors nationally and statewide came together to create a prime environment for implementation of the Baby-Friendly Hospital Initiative. This article will discuss the barriers that one hospital encountered and the strategies used to overcome these common barriers to achieving Baby-Friendly status. This hospital is not yet designated as Baby-Friendly but is awaiting the outcome of a site visit in 2012.

  2. Overcoming of energy barrier for irreversible magnetization in nanocomposite magnets

    NASA Astrophysics Data System (ADS)

    Li, Zhu-bai; Zhang, Ying; Shen, Bao-gen; Zhang, Ming; Hu, Feng-xia; Sun, Ji-rong

    2017-01-01

    The irreversible magnetization occurs mainly in hard grains in nanocomposite magnets, and the domain wall involves a little part of defect region in irreversible magnetization due to the self-interaction. The investigation on thermal activation shows that the defect region involved in domain wall becomes narrower due to the TiNb addition in Pr2Fe14B/α-Fe magnets. The defect region augments the energy density in the negative direction of domain wall to overcome the energy barrier of perfect hard region. The soft phase, exchange-coupled with defect region at hard grain outer-layer, promotes magnetization reversal in defect region by exchange coupling. While the defect region plays a role as a ladder to overcome the energy barrier, resulting in the decrease of coecivity more or less depending upon the width and anisotropy of defect region.

  3. Overcoming barriers to health service access: influencing the demand side.

    PubMed

    Ensor, Tim; Cooper, Stephanie

    2004-03-01

    Evidence suggests that demand-side barriers may be as important as supply factors in deterring patients from obtaining treatment. Yet relatively little attention is given, either by policy makers or researchers, to ways of minimizing their effect. These barriers are likely to be more important for the poor and other vulnerable groups, where the costs of access, lack of information and cultural barriers impede them from benefiting from public spending. Demand barriers present in low- and middle-income countries and evidence on the effectiveness of interventions to overcome these obstacles are reviewed. Demand barriers are also shown to be important in richer countries, particularly among vulnerable groups. This suggests that while barriers are plentiful, there is a dearth of evidence on ways to reduce them. Where evidence does exist, the data and methodology for evaluating effectiveness and cost-effectiveness is insufficient. An increased focus on obtaining robust evidence on effective interventions could yield high returns. The likely nature of the interventions means that pragmatic policy routes that go beyond the traditional boundaries of the public health sector are required for implementing the findings.

  4. Overcoming translational barriers impeding development of Alzheimer's disease modifying therapies.

    PubMed

    Golde, Todd E

    2016-10-01

    It has now been ~ 30 years since the Alzheimer's disease (AD) research entered what may be termed the 'molecular era' that began with the identification of the amyloid β protein (Aβ) as the primary component of amyloid within senile plaques and cerebrovascular amyloid and the microtubule-associated protein tau as the primary component of neurofibrillary tangles in the AD brain. These pivotal discoveries and the subsequent genetic, pathological, and modeling studies supporting pivotal roles for tau and Aβ aggregation and accumulation have provided firm rationale for a new generation of AD therapies designed not to just provide symptomatic benefit, but as disease modifying agents that would slow or even reverse the disease course. Indeed, over the last 20 years numerous therapeutic strategies for disease modification have emerged, been preclinically validated, and advanced through various stages of clinical testing. Unfortunately, no therapy has yet to show significant clinical disease modification. In this review, I describe 10 translational barriers to successful disease modification, highlight current efforts addressing some of these barriers, and discuss how the field could focus future efforts to overcome barriers that are not major foci of current research efforts. Seminal discoveries made over the past 25 years have provided firm rationale for a new generation of Alzheimer's disease (AD) therapies designed as disease modifying agents that would slow or even reverse the disease course. Unfortunately, no therapy has yet to show significant clinical disease modification. In this review, I describe 10 translational barriers to successful AD disease modification, highlight current efforts addressing some of these barriers, and discuss how the field could focus future efforts to overcome these barriers. This article is part of the 60th Anniversary special issue.

  5. Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier

    PubMed Central

    Hersh, David S.; Wadajkar, Aniket S.; Roberts, Nathan B.; Perez, Jimena G.; Connolly, Nina P.; Frenkel, Victor; Winkles, Jeffrey A.; Woodworth, Graeme F.; Kim, Anthony J.

    2016-01-01

    The blood-brain barrier (BBB) poses a unique challenge for drug delivery to the central nervous system (CNS). The BBB consists of a continuous layer of specialized endothelial cells linked together by tight junctions, pericytes, nonfenestrated basal lamina, and astrocytic foot processes. This complex barrier controls and limits the systemic delivery of therapeutics to the CNS. Several innovative strategies have been explored to enhance the transport of therapeutics across the BBB, each with individual advantages and disadvantages. Ongoing advances in delivery approaches that overcome the BBB are enabling more effective therapies for CNS diseases. In this review, we discuss: (1) the physiological properties of the BBB, (2) conventional strategies to enhance paracellular and transcellular transport through the BBB, (3) emerging concepts to overcome the BBB, and (4) alternative CNS drug delivery strategies that bypass the BBB entirely. Based on these exciting advances, we anticipate that in the near future, drug delivery research efforts will lead to more effective therapeutic interventions for diseases of the CNS.

  6. Barriers to women engaging in collective action to overcome sexism.

    PubMed

    Radke, Helena R M; Hornsey, Matthew J; Barlow, Fiona Kate

    2016-12-01

    Over centuries women have fought hard to obtain increasing gender equality, but despite these successes absolute equality remains an elusive goal. Theoretically, women's numerical strength makes them well-placed to take effective collective action, and millions of women engage in feminist collective action every day. In this article, however, we argue that women also face barriers to engaging in feminist collective action; barriers that are associated with the social construction and experience of what it means to be a woman. Our review synthesizes sexism research under a contemporary collective action framework to clarify our current understanding of the literature and to offer novel theoretical explanations for why women might be discouraged from engaging in feminist collective action. Using the antecedents of collective action identified by van Zomeren, Postmes, and Spears' (2008) meta-analysis, we critically review the sexism literature to argue that women face challenges when it comes to (a) identifying with other women and feminists, (b) perceiving sexism and expressing group-based anger, and (c) recognizing the efficacy of collective action. We then outline a research agenda with a view to investigating ways of overcoming these barriers. (PsycINFO Database Record

  7. Overcoming barriers to pain relief in the Caribbean.

    PubMed

    Macpherson, Cheryl; Aarons, Derrick

    2009-12-01

    This paper examines pain and pain relief in the Caribbean, where pain is widely perceived as an unavoidable part of life, and where unnecessary suffering results from untreated and under treated pain. Barriers to pain relief in the Caribbean include patient and family attitudes, inadequate knowledge among health professionals and unduly restrictive regulations on the medical use of opioids. Similar barriers exist all over the world. This paper urges medical, nursing and public health professionals, and educators to examine attitudes towards pain and pain relief and to work towards making effective pain relief and palliation more accessible. It recommends that i) health professionals and officials be better educated about pain, palliation and opioids, ii) regulatory restrictions be updated in light of clinical and scientific evidence, iii) opioid procurement policies be adjusted to facilitate increased medical use, iv) medical charts and records be modified to routinely elicit and document patients levels of pain, and v) educational campaigns be developed to inform the public that moderate and severe pain can be safely relieved at the end of life and other stages of life. The professional, respectful, and beneficent response to patients in pain is to provide rapid and aggressive pain relief or to urgently consult a pain or palliative specialist. When a health system hinders such efforts the ethical response is to identify, facilitate and advocate for overcoming barriers to improvement.

  8. Self-induced dust traps: overcoming planet formation barriers

    NASA Astrophysics Data System (ADS)

    Gonzalez, J.-F.; Laibe, G.; Maddison, S. T.

    2017-01-01

    Planet formation is thought to occur in discs around young stars by the aggregation of small dust grains into much larger objects. The growth from grains to pebbles and from planetesimals to planets is now fairly well understood. The intermediate stage has however been found to be hindered by the radial-drift and fragmentation barriers. We identify a powerful mechanism in which dust overcomes both barriers. Its key ingredients are i) backreaction from the dust onto the gas, ii) grain growth and fragmentation, and iii) large-scale gradients. The pile-up of growing and fragmenting grains modifies the gas structure on large scales and triggers the formation of pressure maxima, in which particles are trapped. We show that these self-induced dust traps are robust: they develop for a wide range of disc structures, fragmentation thresholds and initial dust-to-gas ratios. They are favored locations for pebbles to grow into planetesimals, thus opening new paths towards the formation of planets.

  9. Rotational barriers of biphenyls having heavy heteroatoms as ortho-substituents: experimental and theoretical determination of steric effects.

    PubMed

    Lunazzi, Lodovico; Mancinelli, Michele; Mazzanti, Andrea; Lepri, Susan; Ruzziconi, Renzo; Schlosser, Manfred

    2012-03-07

    The free energies of activation for the aryl-aryl rotation of 17 biphenyl derivatives, bearing a heavy heteroatom (S, Se, Te, P, Si, Sn) as ortho substituent, have been measured by variable temperature NMR. These numbers, so called B values, represent a meaningful measure of the steric hindrance exerted by the selected substituents. DFT computations match quite satisfactorily the experimental barriers and the ground state geometries as well (determined, in two cases, by X-ray diffraction). The present values extend the available list of B values and thus provide an enlarged basis for the compilation of the space requirements of standard substituents, based solely on experimental determinations.

  10. Polymeric nanoparticles of different sizes overcome the cell membrane barrier.

    PubMed

    Lerch, Simone; Dass, Martin; Musyanovych, Anna; Landfester, Katharina; Mailänder, Volker

    2013-06-01

    Polymeric nanoparticles have tremendous potential either as carriers or markers in treatment for diseases or as diagnostics in biomedical applications. Finding the optimal conditions for effective intracellular delivery of the payload to the location of interest is still a big challenge. The particles have to overcome the barrier of the cell membrane. Here, we investigated the uptake in HeLa cells of fluorescent polystyrene particles with different size and surface charge. Particles stabilized with the nonionic surfactant Lutensol AT50® (132 nm, 180 nm, 242 nm, 816 nm, 846 nm diameter) were synthesized via dispersion polymerization. Cationic particles (120 nm, 208 nm, 267 nm, 603 nm diameter) were obtained by a combination of miniemulsion and seed dispersion polymerization using cationic surfactant (cetyltrimethylammonium chloride (CTMA-Cl). The particle uptake into HeLa cells was studied by confocal laser scanning microscopy and flow cytometry. Nonionic particles were - independent of their size - taken up by cells only at a barely detectable level, thus aggravating a quantitative comparison. The uptake of positively charged particles was substantially higher and therefore enabling further investigation keeping constant one of these parameters: either material amount or particles number or total interaction surface area. It was found that the uptake rather depends on the total amount of polymeric material present in the media than on the number of particles. The total particle's surface area does not correlate linearly with the uptake, thus indicating that there is no direct dependency between the total surface area and the cellular endocytotic process to overcome the biobarrier "cell membrane." A potentially novel uptake mechanism is found which can be described as an excavator shovel like mechanism. It is a kind of macropinocytosis dependent on actin filaments as well as dynamin, but is clathrin-independent.

  11. Overcoming barriers to integrating economic analysis into risk assessment.

    PubMed

    Hoffmann, Sandra

    2011-09-01

    Regulatory risk analysis is designed to provide decisionmakers with a clearer understanding of how policies are likely to affect risk. The systems that produce risk are biological, physical, and social and economic. As a result, risk analysis is an inherently interdisciplinary task. Yet in practice, risk analysis has been interdisciplinary in only limited ways. Risk analysis could provide more accurate assessments of risk if there were better integration of economics and other social sciences into risk assessment itself. This essay examines how discussions about risk analysis policy have influenced the roles of various disciplines in risk analysis. It explores ways in which integrated bio/physical-economic modeling could contribute to more accurate assessments of risk. It reviews examples of the kind of integrated economics-bio/physical modeling that could be used to enhance risk assessment. The essay ends with a discussion of institutional barriers to greater integration of economic modeling into risk assessment and provides suggestions on how these might be overcome.

  12. Overcoming Barriers to Wind Development in Appalachian Coal Country

    SciTech Connect

    Brent Bailey; Evan Hansen

    2012-10-09

    This research project synthesizes existing data and communication from experts to assess barriers to wind development in Pennsylvania, Maryland, West Virginia, Virginia, and Kentucky, and makes recommendations where feasible to reduce or eliminate those barriers.

  13. 75 FR 58347 - Information Collection; Overcoming Barriers to Wildland Fire Defensible Space Behaviors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ...; ] DEPARTMENT OF AGRICULTURE Forest Service Information Collection; Overcoming Barriers to Wildland Fire... Fire Defensible Space Behaviors. DATES: Comments must be received in writing on or before November 23...: Overcoming Barriers to Wildland Fire Defensible Space Behaviors. OMB Number: 0596-New. Type of Request:...

  14. SOLUTIONS TO OVERCOME BARRIERS TO IMPLEMENTATION OF TREATMENT TECHNOLOGIES

    EPA Science Inventory

    To make treatment a viable option for remediation you must first identify the barriers to implementing treatment. The primary barrier is economics. Treatment options are relatively expensive and there is a lack of funds for treatment. The cost of technologies can be lowered by 1)...

  15. Teaching English Language Learners: Strategies for Overcoming Barriers

    ERIC Educational Resources Information Center

    Helfrich, Sara R.; Bosh, Amy J.

    2011-01-01

    The number of English language learners (ELLs) in today's classrooms is increasing. In this article, the authors identify four perceived barriers beginning and veteran teachers face in teaching literacy to ELLs: the lack of understanding of the role of literacy in other cultures, the teacher's inability to differentiate instruction to meet the…

  16. Automation U.S.A.: Overcoming Barriers to Automation.

    ERIC Educational Resources Information Center

    Brody, Herb

    1985-01-01

    Although labor unions and inadequate technology play minor roles, the principal barrier to factory automation is "fear of change." Related problems include long-term benefits, nontechnical executives, and uncertainty of factory cost accounting. Industry support for university programs is helping to educate engineers to design, implement, and…

  17. Adolescents' Self-Efficacy to Overcome Barriers to Physical Activity Scale

    ERIC Educational Resources Information Center

    Dwyer, John J. M.; Chulak, Tala; Maitland, Scott; Allison, Kenneth R.; Lysy, Daria C.; Faulkner, Guy E. J.; Sheeshka, Judy

    2012-01-01

    This paper describes a revised measure of self-efficacy to overcome barriers to moderate and vigorous physical activity in a sample of 484 high school students in Toronto, Ontario. The students had a mean age of 15.3 years. Principal axis factoring with oblique rotation yielded five factors: self-efficacy to overcome internal, harassment, physical…

  18. Overcoming barriers in online workshop development: an ELITE experience.

    PubMed

    Talcott, Kimberly S; O'Donnell, John M; Burns, Helen K

    2013-06-01

    The Emerging Learning and Integrated Technologies Education (ELITE) Faculty Development Program created eight online workshops to assist nurse educators in using technology within their organization's nurse education program. Continuing education units were provided for completion of the individual online workshops. The ELITE program worked through several barriers to transform content that was previously presented during face-to-face workshops into standalone online offerings. Barriers and implementation strategies for the on-site to online transition included restructuring workshop objectives, keeping current with rapid technology changes, altering a course management system to meet the needs of the program and the learner, and crafting independent practice opportunities for the online learner. The online workshop development experience of the ELITE program may assist other continuing education and staff development professionals who are updating their program offerings or pursuing online education for the first time.

  19. Implementing District Energy Systems: Municipal Approaches To Overcoming Barriers

    NASA Astrophysics Data System (ADS)

    Simpson, Kevin George

    Climate change and energy security are issues facing municipalities throughout the world. Efficient, resilient, sustainable, community-based energy systems, such as district energy systems (DES), fuelled mostly by renewables, are an important tool for addressing both climate change and energy security at the municipal level. In spite of their benefits, DES are not widely adopted in Canada (CDEA, 2011). This is due to the complex nature of the barriers which project proponents face. This thesis examines the experience of the City of Prince George in adopting and implementing the Downtown DES. Using a case study methodology, data was collected through a review of relevant municipal documents and a series of semi-structured, open-ended interviews. A thematic analysis revealed unexpected barriers related to lack of adequate public consultation and negative perceptions regarding biomass as a fuel for the DES. These `lessons learned' were then developed into recommendations for other municipalities considering DES.

  20. No One Is Unemployable: Creative Solutions for Overcoming Barriers to Employment.

    ERIC Educational Resources Information Center

    Harney, Elisabeth E.

    The goal of the WorkNet Model Career Development & Job Placement for people with barriers is to help even the most challenged job seekers begin and advance in careers they enjoy. This paper presents one key component of the WorkNet Model, a practical process for creatively overcoming any barrier a candidate faces. The chapter includes: the…

  1. Overcoming barriers to public understanding of climate change

    NASA Astrophysics Data System (ADS)

    Hayhoe, K.

    2012-12-01

    Humans are interfering with global climate, increasing the risk of serious consequences for human society and the natural environment. As the scientific evidence builds, however, so does the public controversy surrounding this issue. Why is climate change so contentious? What makes it so hard to comprehend? I argue that there is no single reason for this, but rather a perfect storm of multiple confounding factors; scientific, historical, ideological, psychological and even physiological in nature. Education—of both the messengers and the audience—can play a critical role in surmounting many of the common barriers to understanding, accepting, and acting this important issue.

  2. Overcoming the barriers to using kangaroo care in neonatal settings.

    PubMed

    Penn, Sarah

    2015-06-01

    Skin-to-skin contact, or kangaroo care (KC), has benefits for babies and parents, improving clinical outcomes, temperature control, breastfeeding rates and child-parent bonding; it reduces morbidity and mortality. Barriers to KC for neonates may include a lack of training for nurses, lack of time, maternal or child physical or mental ill health, and inappropriate settings. With education and helpful management, neonatal nurses can advocate for KC for all babies. Parents may need information and encouragement to begin with. Therefore, nurses can improve the experiences of their patients and, in the long run, free time to perform clinical procedures.

  3. Kidney Exchange to Overcome Financial Barriers to Kidney Transplantation.

    PubMed

    Rees, M A; Dunn, T B; Kuhr, C S; Marsh, C L; Rogers, J; Rees, S E; Cicero, A; Reece, L J; Roth, A E; Ekwenna, O; Fumo, D E; Krawiec, K D; Kopke, J E; Jain, S; Tan, M; Paloyo, S R

    2017-03-01

    Organ shortage is the major limitation to kidney transplantation in the developed world. Conversely, millions of patients in the developing world with end-stage renal disease die because they cannot afford renal replacement therapy-even when willing living kidney donors exist. This juxtaposition between countries with funds but no available kidneys and those with available kidneys but no funds prompts us to propose an exchange program using each nation's unique assets. Our proposal leverages the cost savings achieved through earlier transplantation over dialysis to fund the cost of kidney exchange between developed-world patient-donor pairs with immunological barriers and developing-world patient-donor pairs with financial barriers. By making developed-world health care available to impoverished patients in the developing world, we replace unethical transplant tourism with global kidney exchange-a modality equally benefitting rich and poor. We report the 1-year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor's kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow-up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable.

  4. Physical activity and exercise after stoma surgery: overcoming the barriers.

    PubMed

    Russell, Sarah

    2017-03-09

    This article presents the results from a large nationwide survey completed in 2016 that investigated the physical health and wellbeing of people living with stomas in the UK. In particular, the survey looked at physical activity and exercise, general attitudes and opinions about exercise, whether or not advice about physical activity had been received and other general questions about parastomal hernia and quality of life. There were 2631 respondents making it one of the largest known surveys to date. The findings were concerning yet unsurprising, highlighting a trend toward inactivity after stoma surgery and a fear of exercise in general. People also seem to have poor knowledge about appropriate activities, with many suggesting that the fear of developing a parastomal hernia is a major barrier to activity. Unsurprisingly, those who have a stoma owing to cancer seem to fare worse, reporting even lower levels of physical activity and worse quality of life compared to those with other conditions. This indicates that people who have a combination of a cancer diagnosis and also a stoma may need more specific or additional support in the longer term. The most concerning finding, however, was that the majority of patients could not recall being given any advice about exercise or physical activity by their nurse or surgeon. While this survey presents some initial findings, it raises questions for further research and work. It also highlights a significantly neglected area in both research and support for stoma patients and the health professionals caring for them.

  5. Mentoring women in academic surgery: overcoming institutional barriers to success.

    PubMed

    Hoover, Eddie L

    2006-09-01

    Women now comprise 50% of Caucasian matriculants to medical school; 66.6% of African Americans, 48% of Hispanics and 51.3% of Asians beginning medical school are also women. This trend is likely to continue since women now earn 57% of all undergraduate degrees, and they earn more degrees in the health professions and biological sciences than men. Black and Hispanic women now earn 66% and 60% of bachelor's degrees in their respective ethnic groups. Overall, women are concentrated at the lowest faculty ranks at medical schools, with 70% holding the rank of instructor or assistant professor. Women continue to experience difficulty with recruitment, retention, promotion and pay issues compared to men. They also experience additional gender-specific issues, including primary responsibility for rearing families and quality-of-life issues in some specialties, including most of the surgical disciplines. Clearly, there is an evolving population shift at work here; the pool of candidates for medical school faculty positions is likely to be evenly split between men and women for Caucasians, Hispanics and Asians, while the African-American pool is likely heavily weighted in favor of the women. Women are beginning to garner more Latin honors recognition at graduation as well and the definition of the "best and the brightest" is being redefined. Therefore, institutions must continue to identify the barriers that deter women from entering surgery, to develop research tools to understand how to improve the process of developing leadership skills among women and to insure a "buy-in" of their male counterparts when components of the plan are being implemented.

  6. Coherent anti-Stokes Raman scattering microscopy: overcoming technical barriers for clinical translation.

    PubMed

    Tu, Haohua; Boppart, Stephen A

    2014-01-01

    Clinical translation of coherent anti-Stokes Raman scattering microscopy is of great interest because of the advantages of noninvasive label-free imaging, high sensitivity, and chemical specificity. For this to happen, we have identified and review the technical barriers that must be overcome. Prior investigations have developed advanced techniques (features), each of which can be used to effectively overcome one particular technical barrier. However, the implementation of one or a small number of these advanced features in previous attempts for clinical translation has often introduced more tradeoffs than benefits. In this review, we outline a strategy that would integrate multiple advanced features to overcome all the technical barriers simultaneously, effectively reduce tradeoffs, and synergistically optimize CARS microscopy for clinical translation. The operation of the envisioned system incorporates coherent Raman micro-spectroscopy for identifying vibrational biomolecular markers of disease and single-frequency (or hyperspectral) Raman imaging of these specific biomarkers for real-time in vivo diagnostics and monitoring.

  7. Overcoming Barriers to Skills Training in Borderline Personality Disorder: A Qualitative Interview Study.

    PubMed

    Barnicot, Kirsten; Couldrey, Laura; Sandhu, Sima; Priebe, Stefan

    2015-01-01

    Despite evidence suggesting that skills training is an important mechanism of change in dialectical behaviour therapy, little research exploring facilitators and barriers to this process has been conducted. The study aimed to explore clients' experiences of barriers to dialectical behaviour therapy skills training and how they felt they overcame these barriers, and to compare experiences between treatment completers and dropouts. In-depth qualitative interviews were conducted with 40 clients with borderline personality disorder who had attended a dialectical behaviour therapy programme. A thematic analysis of participants' reported experiences found that key barriers to learning the skills were anxiety during the skills groups and difficulty understanding the material. Key barriers to using the skills were overwhelming emotions which left participants feeling unable or unwilling to use them. Key ways in which participants reported overcoming barriers to skills training were by sustaining their commitment to attending therapy and practising the skills, personalising the way they used them, and practising them so often that they became an integral part of their behavioural repertoire. Participants also highlighted a number of key ways in which they were supported with their skills training by other skills group members, the group therapists, their individual therapist, friends and family. Treatment dropouts were more likely than completers to describe anxiety during the skills groups as a barrier to learning, and were less likely to report overcoming barriers to skills training via the key processes outlined above. The findings of this qualitative study require replication, but could be used to generate hypotheses for testing in further research on barriers to skills training, how these relate to dropout, and how they can be overcome. The paper outlines several such suggestions for further research.

  8. Overcoming Barriers to Skills Training in Borderline Personality Disorder: A Qualitative Interview Study

    PubMed Central

    Barnicot, Kirsten; Couldrey, Laura; Sandhu, Sima; Priebe, Stefan

    2015-01-01

    Despite evidence suggesting that skills training is an important mechanism of change in dialectical behaviour therapy, little research exploring facilitators and barriers to this process has been conducted. The study aimed to explore clients’ experiences of barriers to dialectical behaviour therapy skills training and how they felt they overcame these barriers, and to compare experiences between treatment completers and dropouts. In-depth qualitative interviews were conducted with 40 clients with borderline personality disorder who had attended a dialectical behaviour therapy programme. A thematic analysis of participants’ reported experiences found that key barriers to learning the skills were anxiety during the skills groups and difficulty understanding the material. Key barriers to using the skills were overwhelming emotions which left participants feeling unable or unwilling to use them. Key ways in which participants reported overcoming barriers to skills training were by sustaining their commitment to attending therapy and practising the skills, personalising the way they used them, and practising them so often that they became an integral part of their behavioural repertoire. Participants also highlighted a number of key ways in which they were supported with their skills training by other skills group members, the group therapists, their individual therapist, friends and family. Treatment dropouts were more likely than completers to describe anxiety during the skills groups as a barrier to learning, and were less likely to report overcoming barriers to skills training via the key processes outlined above. The findings of this qualitative study require replication, but could be used to generate hypotheses for testing in further research on barriers to skills training, how these relate to dropout, and how they can be overcome. The paper outlines several such suggestions for further research. PMID:26465757

  9. Measuring women's perceived ability to overcome barriers to healthcare seeking in Burkina Faso

    PubMed Central

    2012-01-01

    Background In sub-Saharan Africa, women must overcome numerous barriers when they need modern healthcare. Respect of gender norms within the household and the community may still influence women's ability to obtain care. A lack of gender-sensitive instruments for measuring women's ability to overcome barriers compromises attempts to adequately quantify the burden and risk of exclusion they face when seeking modern healthcare. The aim of this study was to create and validate a synthetic measure of women's access to healthcare from a publicly available and possibly internationally comparable population-based survey. Method Seven questionnaire items from the Burkina Faso 2003 DHS were combined to create the index. Cronbach's alpha coefficient was used to test the reliability of the index. Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were applied to evaluate the factorial structure and construct validity of the index while taking into account the hierarchical structure of the data. Results The index has a Cronbach's alpha of 0.75, suggesting adequate reliability. In EFA, three correlated factors fitted the data best. In CFA, the construct of perceived ability to overcome barriers to healthcare seeking emerged as a second-order latent variable with three domains: socioeconomic barriers, geographical barriers and psychosocial barriers. Model fit indices support the index's global validity for women of reproductive age in Burkina Faso. Evidence for construct validity comes from the finding that women's index scores increase with household living standard. Conclusion The DHS items can be combined into a reliable and valid, gender-sensitive index quantifying reproductive-age women's perceived ability to overcome barriers to healthcare seeking in Burkina Faso. The index complies conceptually with the sector-cross-cutting capability approach and enables measuring directly the perceived access to healthcare. Therefore it can help to improve the

  10. Strategies for Overcoming Key Barriers to Development of a National Security Workforce

    SciTech Connect

    2008-06-30

    This report documents the strategies for overcoming identified key barriers to development of an adequate national security workforce as part of the National Security Preparedness Project (NSPP) being performed under a Department of Energy (DOE) National Nuclear Security Administration (NNSA) grant. Many barriers currently exist that prevent the development of an adequate number of properly trained national security personnel. The identified strategies to address the barriers will focus on both short-term and long-term efforts, as well as strategies to capture legacy knowledge of retiring national security workforce personnel.

  11. Building America Guidance for Identifying and Overcoming Code, Standard, and Rating Method Barriers

    SciTech Connect

    Cole, P. C.; Halverson, M. A.

    2013-09-01

    This guidance document was prepared using the input from the meeting summarized in the draft CSI Roadmap to provide Building America research teams and partners with specific information and approaches to identifying and overcoming potential barriers to Building America innovations arising in and/or stemming from codes, standards, and rating methods.

  12. Using Appropriate Digital Tools to Overcome Barriers to Collaborative Learning in Classrooms

    ERIC Educational Resources Information Center

    Wardlow, Liane; Harm, Eian

    2015-01-01

    Collaborative learning provides students with vital opportunities to create and build knowledge. Existing technologies can facilitate collaborative learning. However, barriers exist to enacting collaborative practices related to the coverage of material for assessments and classroom management concerns, among others. Teachers can overcome these…

  13. Critical elements for eco-retrofitting a conventional industrial park: Social barriers to be overcome.

    PubMed

    Ceglia, Domenico; Abreu, Mônica Cavalcanti Sá de; Da Silva Filho, José Carlos Lázaro

    2017-02-01

    This paper aims to explore critical elements for eco-retrofitting a conventional industrial park, based on a survey of companies and institutions located in Brazil. The study investigates social barriers to be overcome in promotion of opportunities for waste exchange. Our results indicate that values, trust behaviour, waste cognitive domain and environment engagement are necessary for the creation of an eco-industrial park. Similar values of benevolence and universalism are essential for company engagement to eco-retrofit. Low levels of trust behaviour combining with limited waste cognitive domain prevent firms from establishing agreement on waste exchange initiatives. The findings lend support to the view that social barriers are pre-requisites to engagement among firms in establishing technological and logistical solutions. Serious attention needs to be given to these social barriers because they are not easily overcome in the social and economic context of developing countries.

  14. Identifying and Overcoming Barriers to Diabetes Management in the Elderly: An Intervention Study

    DTIC Science & Technology

    2010-06-01

    research period, we have nearly completed recruitment of patients over age 70 with diabetes and poor glycemic control as defined by A1c>8%, and have...older adults even with poor glycemic control. 2) Self-management interventions to overcome barriers to diabetes improved self-care frequency and...continuous glucose monitoring. 15. SUBJECT TERMS Diabetes, elderly, glycemic control, Cerebral perfusion, Care management 16. SECURITY

  15. Overcoming the Cystic Fibrosis Sputum Barrier to Leading Adeno-associated Virus Gene Therapy Vectors

    PubMed Central

    Schuster, Benjamin S; Kim, Anthony J; Kays, Joshua C; Kanzawa, Mia M; Guggino, William B; Boyle, Michael P; Rowe, Steven M; Muzyczka, Nicholas; Suk, Jung Soo; Hanes, Justin

    2014-01-01

    Gene therapy has not yet improved cystic fibrosis (CF) patient lung function in human trials, despite promising preclinical studies. In the human CF lung, inhaled gene vectors must penetrate the viscoelastic secretions coating the airways to reach target cells in the underlying epithelium. We investigated whether CF sputum acts as a barrier to leading adeno-associated virus (AAV) gene vectors, including AAV2, the only serotype tested in CF clinical trials, and AAV1, a leading candidate for future trials. Using multiple particle tracking, we found that sputum strongly impeded diffusion of AAV, regardless of serotype, by adhesive interactions and steric obstruction. Approximately 50% of AAV vectors diffused >1,000-fold more slowly in sputum than in water, with large patient-to-patient variation. We thus tested two strategies to improve AAV diffusion in sputum. We showed that an AAV2 mutant engineered to have reduced heparin binding diffused twice as fast as AAV2 on average, presumably because of reduced adhesion to sputum. We also discovered that the mucolytic N-acetylcysteine could markedly enhance AAV diffusion by altering the sputum microstructure. These studies underscore that sputum is a major barrier to CF gene delivery, and offer strategies for increasing AAV penetration through sputum to improve clinical outcomes. PMID:24869933

  16. "Closing the Loop": Overcoming barriers to locally sourcing food in Fort Collins, Colorado

    NASA Astrophysics Data System (ADS)

    DeMets, C. M.

    2012-12-01

    Environmental sustainability has become a focal point for many communities in recent years, and restaurants are seeking creative ways to become more sustainable. As many chefs realize, sourcing food locally is an important step towards sustainability and towards building a healthy, resilient community. Review of literature on sustainability in restaurants and the local food movement revealed that chefs face many barriers to sourcing their food locally, but that there are also many solutions for overcoming these barriers that chefs are in the early stages of exploring. Therefore, the purpose of this research is to identify barriers to local sourcing and investigate how some restaurants are working to overcome those barriers in the city of Fort Collins, Colorado. To do this, interviews were conducted with four subjects who guide purchasing decisions for restaurants in Fort Collins. Two of these restaurants have created successful solutions and are able to source most of their food locally. The other two are interested in and working towards sourcing locally but have not yet been able to overcome barriers, and therefore only source a few local items. Findings show that there are four barriers and nine solutions commonly identified by each of the subjects. The research found differences between those who source most of their food locally and those who have not made as much progress in local sourcing. Based on these results, two solution flowcharts were created, one for primary barriers and one for secondary barriers, for restaurants to assess where they are in the local food chain and how they can more successfully source food locally. As there are few explicit connections between this research question and climate change, it is important to consider the implicit connections that motivate and justify this research. The question of whether or not greenhouse gas emissions are lower for locally sourced food is a topic of much debate, and while there are major developments

  17. Designing Caregiver-Implemented Shared-Reading Interventions to Overcome Implementation Barriers

    PubMed Central

    Logan, Jessica R.; Damschroder, Laura

    2015-01-01

    Purpose This study presents an application of the theoretical domains framework (TDF; Michie et al., 2005), an integrative framework drawing on behavior-change theories, to speech-language pathology. Methods A multistep procedure was used to identify barriers affecting caregivers' implementation of shared-reading interventions with their children with language impairment (LI). The authors examined caregiver-level data corresponding to implementation issues from two randomized controlled trials and mapped these to domains in the TDF as well as empirically validated behavior-change techniques. Results Four barriers to implementation were identified as potentially affecting caregivers' implementation: time pressures, reading difficulties, discomfort with reading, and lack of awareness of benefits. These were mapped to 3 TDF domains: intentions, beliefs about capabilities, and skills. In turn, 4 behavior-change techniques were identified as potential vehicles for affecting these domains: reward, feedback, model, and encourage. An ongoing study is described that is determining the effects of these techniques for improving caregivers' implementation of a shared-reading intervention. Conclusions A description of the steps to identifying barriers to implementation, in conjunction with an ongoing experiment that will explicitly determine whether behavior-change techniques affect these barriers, provides a model for how implementation science can be used to identify and overcome implementation barriers in the treatment of communication disorders. PMID:26262941

  18. Geothermal(Ground-Source)Heat Pumps: Market Status, Barriers to Adoption, and Actions to Overcome Barriers

    SciTech Connect

    Hughes, Patrick

    2008-12-01

    More effective stewardship of our resources contributes to the security, environmental sustainability, and economic well-being of the nation. Buildings present one of the best opportunities to economically reduce energy consumption and limit greenhouse gas emissions. Geothermal heat pumps (GHPs), sometimes called ground-source heat pumps, have been proven capable of producing large reductions in energy use and peak demand in buildings. However, GHPs have received little attention at the policy level as an important component of a national strategy. Have policymakers mistakenly overlooked GHPs, or are GHPs simply unable to make a major contribution to the national goals for various reasons? This brief study was undertaken at DOE's request to address this conundrum. The scope of the study includes determining the status of global GHP markets and the status of the GHP industry and technology in the United States, assembling previous estimates of GHP energy savings potential, identifying key barriers to application of GHPs, and identifying actions that could accelerate market adoption of GHPs. The findings are documented in this report along with conclusions and recommendations.

  19. Hedgehog Signaling Overcomes an EZH2-Dependent Epigenetic Barrier to Promote Cholangiocyte Expansion

    PubMed Central

    Lu, Jie; Almada, Luciana L.; Lomberk, Gwen; Fernandez-Zapico, Martin E.; Urrutia, Raul; Huebert, Robert C.

    2016-01-01

    Background & Aims Developmental morphogens play an important role in coordinating the ductular reaction and portal fibrosis occurring in the setting of cholangiopathies. However, little is known about how membrane signaling events in ductular reactive cells (DRCs) are transduced into nuclear transcriptional changes to drive cholangiocyte maturation and matrix deposition. Therefore, the aim of this study was to investigate potential mechanistic links between cell signaling events and epigenetic regulators in DRCs. Methods Using directed differentiation of induced pluripotent stem cells (iPSC), isolated DRCs, and in vivo models, we examine the mechanisms whereby sonic hedgehog (Shh) overcomes an epigenetic barrier in biliary precursors and promotes both cholangiocyte maturation and deposition of fibronectin (FN). Results We demonstrate, for the first time, that Gli1 influences the differentiation state and fibrogenic capacity of iPSC-derived hepatic progenitors and isolated DRCs. We outline a novel pathway wherein Shh-mediated Gli1 binding in key cholangiocyte gene promoters overcomes an epigenetic barrier conferred by the polycomb protein, enhancer of zeste homolog 2 (EZH2) and initiates the transcriptional program of cholangiocyte maturation. We also define previously unknown functional Gli1 binding sites in the promoters of cytokeratin (CK)7, CK19, and FN. Our in vivo results show that EZH2 KO mice fed the choline-deficient, ethanolamine supplemented (CDE) diet have an exaggerated cholangiocyte expansion associated with more robust ductular reaction and increased peri-portal fibrosis. Conclusion We conclude that Shh/Gli1 signaling plays an integral role in cholangiocyte maturation in vitro by overcoming an EZH2-dependent epigenetic barrier and this mechanism also promotes biliary expansion in vivo. PMID:27936185

  20. Overcoming barriers in topical administration of gold nanoparticles for optical coherence tomography using multimodal delivery

    NASA Astrophysics Data System (ADS)

    Kim, Chang Soo; Wilder-Smith, Petra; Ahn, Yeh-Chan; Liaw, Lih-Huei L.; Chen, Zhongping; Kwon, Young Jik

    2010-02-01

    Optical coherence tomography (OCT) is a non-invasive and promising imaging modality with high resolution that is an order of magnitude higher than current diagnostic techniques. However, its use in detecting early-stage cancer is limited due to insufficient contrast level in biological tissue, which can be enhanced by harnessing contrast agents [e.g., gold nanoparticles (Au NPs)]. Enhanced penetration by creating micropassages and distribution by ultrasonic force (multimodal topical delivery) was proven to overcome two major barriers (stratum corneum and epithelial barriers) in topically administering Au NPs using an in vivo oral dysplasia hamster model (overall 150% enhanced OCT contrast). Expanded progress on a highly efficient and versatile Au NP-releasing polymer microneedle platform showed a promising next generation multi-modal delivery of Au NPs.

  1. Overcoming barriers to high performance seismic design using lessons learned from the green building industry

    NASA Astrophysics Data System (ADS)

    Glezil, Dorothy

    NEHRP's Provisions today currently governing conventional seismic resistant design. These provisions, though they ensure the life-safety of building occupants, extensive damage and economic losses may still occur in the structures. This minimum performance can be enhanced using the Performance-Based Earthquake Engineering methodology and passive control systems like base isolation and energy dissipation systems. Even though these technologies and the PBEE methodology are effective reducing economic losses and fatalities during earthquakes, getting them implemented into seismic resistant design has been challenging. One of the many barriers to their implementation has been their upfront costs. The green building community has faced some of the same challenges that the high performance seismic design community currently faces. The goal of this thesis is to draw on the success of the green building industry to provide recommendations that may be used overcome the barriers that high performance seismic design (HPSD) is currently facing.

  2. Smart nanoparticles improve therapy for drug-resistant tumors by overcoming pathophysiological barriers

    PubMed Central

    Liu, Jian-ping; Wang, Ting-ting; Wang, Dang-ge; Dong, An-jie; Li, Ya-ping; Yu, Hai-jun

    2017-01-01

    The therapeutic outcome of chemotherapy is severely limited by intrinsic or acquired drug resistance, the most common causes of chemotherapy failure. In the past few decades, advancements in nanotechnology have provided alternative strategies for combating tumor drug resistance. Drug-loaded nanoparticles (NPs) have several advantages over the free drug forms, including reduced cytotoxicity, prolonged circulation in the blood and increased accumulation in tumors. Currently, however, nanoparticulate drugs have only marginally improved the overall survival rate in clinical trials because of the various pathophysiological barriers that exist in the tumor microenvironment, such as intratumoral distribution, penetration and intracellular trafficking, etc. Smart NPs with stimulus-adaptable physico-chemical properties have been extensively developed to improve the therapeutic efficacy of nanomedicine. In this review, we summarize the recent advances of employing smart NPs to treat the drug-resistant tumors by overcoming the pathophysiological barriers in the tumor microenvironment. PMID:27569390

  3. Overcoming Codes and Standards Barriers to Innovations in Building Energy Efficiency

    SciTech Connect

    Cole, Pamala C.; Gilbride, Theresa L.

    2015-02-15

    In this journal article, the authors discuss approaches to overcoming building code barriers to energy-efficiency innovations in home construction. Building codes have been a highly motivational force for increasing the energy efficiency of new homes in the United States in recent years. But as quickly as the codes seem to be changing, new products are coming to the market at an even more rapid pace, sometimes offering approaches and construction techniques unthought of when the current code was first proposed, which might have been several years before its adoption by various jurisdictions. Due to this delay, the codes themselves can become barriers to innovations that might otherwise be helping to further increase the efficiency, comfort, health or durability of new homes. . The U.S. Department of Energy’s Building America, a program dedicated to improving the energy efficiency of America’s housing stock through research and education, is working with the U.S. housing industry through its research teams to help builders identify and remove code barriers to innovation in the home construction industry. The article addresses several approaches that builders use to achieve approval for innovative building techniques when code barriers appear to exist.

  4. Adaptation of avian influenza A virus polymerase in mammals to overcome the host species barrier.

    PubMed

    Mänz, Benjamin; Schwemmle, Martin; Brunotte, Linda

    2013-07-01

    Avian influenza A viruses, such as the highly pathogenic avian H5N1 viruses, sporadically enter the human population but often do not transmit between individuals. In rare cases, however, they establish a new lineage in humans. In addition to well-characterized barriers to cell entry, one major hurdle which avian viruses must overcome is their poor polymerase activity in human cells. There is compelling evidence that these viruses overcome this obstacle by acquiring adaptive mutations in the polymerase subunits PB1, PB2, and PA and the nucleoprotein (NP) as well as in the novel polymerase cofactor nuclear export protein (NEP). Recent findings suggest that synthesis of the viral genome may represent the major defect of avian polymerases in human cells. While the precise mechanisms remain to be unveiled, it appears that a broad spectrum of polymerase adaptive mutations can act collectively to overcome this defect. Thus, identification and monitoring of emerging adaptive mutations that further increase polymerase activity in human cells are critical to estimate the pandemic potential of avian viruses.

  5. Overcoming the Barriers to Pharmacist Intervention in Problems Associated with the Use of Drugs--Institutional Pharmacy.

    ERIC Educational Resources Information Center

    Baumgartner, R. Paul, Jr.

    1979-01-01

    Barriers to role expansion for pharmacists working in institutional settings are discussed, such as competency, interdisciplinary responsibilities, and financial reimbursement. Underlying principles that may be applied to overcome the traditional barriers to pharmacist intervention in drug use problems are examined. (SF)

  6. Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier.

    PubMed

    Di Gioia, Sante; Trapani, Adriana; Castellani, Stefano; Carbone, Annalucia; Belgiovine, Giuliana; Craparo, Emanuela Fabiola; Puglisi, Giovanni; Cavallaro, Gennara; Trapani, Giuseppe; Conese, Massimo

    2015-10-01

    Gene therapy, i.e. the delivery and expression of therapeutic genes, holds great promise for congenital and acquired respiratory diseases. Non-viral vectors are less toxic and immunogenic than viral vectors, although they are characterized by lower efficiency. However, they have to overcome many barriers, including inflammatory and immune mediators and cells. The respiratory and airway epithelial cells, the main target of these vectors, are coated with a layer of mucus, which hampers the effective reaching of gene therapy vectors carrying either plasmid DNA or small interfering RNA. This barrier is thicker in many lung diseases, such as cystic fibrosis. This review summarizes the most important advancements in the field of non-viral vectors that have been achieved with the use of nanoparticulate (NP) systems, composed either of polymers or lipids, in the lung gene delivery. In particular, different strategies of targeting of respiratory and airway lung cells will be described. Then, we will focus on the two approaches that attempt to overcome the mucus barrier: coating of the nanoparticulate system with poly(ethylene glycol) and treatment with mucolytics. Our conclusions are: 1) Ligand and physical targeting can direct therapeutic gene expression in specific cell types in the respiratory tract; 2) Mucopenetrating NPs are endowed with promising features to be useful in treating respiratory diseases and should be now advanced in pre-clinical trials. Finally, we discuss the development of such polymer- and lipid-based NPs in the context of in vitro and in vivo disease models, such as lung cancer, as well as in clinical trials.

  7. Overcoming Barriers: Adolescents’ Experiences Using a Mobile Phone Dietary Assessment App

    PubMed Central

    Svensson, Åsa; Magnusson, Maria

    2016-01-01

    Background The use of new technology has the potential to increase participation rates in dietary studies and improve the validity of collected dietary data. However, to evaluate the usability of developed dietary methods, qualitative studies of participants’ experiences and perceptions are needed. Objective To explore adolescents’ experiences using a newly developed mobile phone dietary assessment app, with a focus on factors that could affect their recording of dietary intake. Methods Focus group interviews were conducted with 75 participants who had used a newly developed mobile phone dietary assessment app in a quantitative evaluation study. The interviews were analyzed using qualitative content analysis and the theoretical framework of Self Determination Theory was applied. Results The adolescents’ use of the mobile phone dietary assessment app was characterized by their struggle to overcome several perceived barriers. Facilitators that helped adolescents complete the method were also identified. Motivation was found to be an important facilitator, and intrinsically motivated participants completed the method because they found it fun to use. The autonomous extrinsically motivated participants completed the method for the greater good, in order to contribute to the study. The controlled extrinsically motivated participants completed the method to get a reward or avoid punishment. Amotivated participants did not complete the method. More motivated participants were assumed to be more able to overcome barriers and needed less facilitators. Conclusions Future studies that examine the recording of food intake should include systematic efforts that aim to minimize identified barriers and promote identified facilitators. Further research should specifically aim at studying methods for (and effects of) increasing intrinsic motivation by supporting autonomy, competence, and relatedness among adolescents asked to participate in dietary studies. PMID:27473462

  8. Preparing Dental Students and Residents to Overcome Internal and External Barriers to Evidence-Based Practice.

    PubMed

    Coleman, Brandon G; Johnson, Thomas M; Erley, Kenneth J; Topolski, Richard; Rethman, Michael; Lancaster, Douglas D

    2016-10-01

    In recent years, evidence-based dentistry has become the ideal for research, academia, and clinical practice. However, barriers to implementation are many, including the complexity of interpreting conflicting evidence as well as difficulties in accessing it. Furthermore, many proponents of evidence-based care seem to assume that good evidence consistently exists and that clinicians can and will objectively evaluate data so as to apply the best evidence to individual patients' needs. The authors argue that these shortcomings may mislead many clinicians and that students should be adequately prepared to cope with some of the more complex issues surrounding evidence-based practice. Cognitive biases and heuristics shape every aspect of our lives, including our professional behavior. This article reviews literature from medicine, psychology, and behavioral economics to explore the barriers to implementing evidence-based dentistry. Internal factors include biases that affect clinical decision making: hindsight bias, optimism bias, survivor bias, and blind-spot bias. External factors include publication bias, corporate bias, and lack of transparency that may skew the available evidence in the peer-reviewed literature. Raising awareness of how these biases exert subtle influence on decision making and patient care can lead to a more nuanced discussion of addressing and overcoming barriers to evidence-based practice.

  9. Teams, tribes and patient safety: overcoming barriers to effective teamwork in healthcare.

    PubMed

    Weller, Jennifer; Boyd, Matt; Cumin, David

    2014-03-01

    Modern healthcare is delivered by multidisciplinary, distributed healthcare teams who rely on effective teamwork and communication to ensure effective and safe patient care. However, we know that there is an unacceptable rate of unintended patient harm, and much of this is attributed to failures in communication between health professionals. The extensive literature on teams has identified shared mental models, mutual respect and trust and closed-loop communication as the underpinning conditions required for effective teams. However, a number of challenges exist in the healthcare environment. We explore these in a framework of educational, psychological and organisational challenges to the development of effective healthcare teams. Educational interventions can promote a better understanding of the principles of teamwork, help staff understand each other's roles and perspectives, and help develop specific communication strategies, but may not be sufficient on their own. Psychological barriers, such as professional silos and hierarchies, and organisational barriers such as geographically distributed teams, can increase the chance of communication failures with the potential for patient harm. We propose a seven-step plan to overcome the barriers to effective team communication that incorporates education, psychological and organisational strategies. Recent evidence suggests that improvement in teamwork in healthcare can lead to significant gains in patient safety, measured against efficiency of care, complication rate and mortality. Interventions to improve teamwork in healthcare may be the next major advance in patient outcomes.

  10. Peptide modules for overcoming barriers of nucleic acids transport to cells.

    PubMed

    Egorova, Anna A; Kiselev, Anton V

    2016-01-01

    Absence of safe and efficient methods of nucleic acids delivery is one of the major issues which limits the development of human gene therapy. Highly efficient viral vectors raise questions due to safety reasons. Among non-viral vectors peptide-based carriers can be considered as good candidates for the development of "artificial viruses"--multifunctional polyplexes that mimic viruses. Suggested strategy to obtain multifunctionality is to combine several peptide modules into one modular carrier. Different kinds of peptide modules are needed for successful overcoming barriers of nucleic acids transport into the cells. Design of such modules and establishment of structure-function relationships are issues of importance to researchers working in the field of nucleic acids delivery.

  11. Building America Guidance for Identifying and Overcoming Code, Standard, and Rating Method Barriers

    SciTech Connect

    Cole, Pamala C.; Halverson, Mark A.

    2013-09-01

    The U.S. Department of Energy’s (DOE) Building America program implemented a new Codes and Standards Innovation (CSI) Team in 2013. The Team’s mission is to assist Building America (BA) research teams and partners in identifying and resolving conflicts between Building America innovations and the various codes and standards that govern the construction of residences. A CSI Roadmap was completed in September, 2013. This guidance document was prepared using the information in the CSI Roadmap to provide BA research teams and partners with specific information and approaches to identifying and overcoming potential barriers to Building America (BA) innovations arising in and/or stemming from codes, standards, and rating methods. For more information on the BA CSI team, please email: CSITeam@pnnl.gov

  12. N-trimethyl chitosan chloride-coated PLGA nanoparticles overcoming multiple barriers to oral insulin absorption.

    PubMed

    Sheng, Jianyong; Han, Limei; Qin, Jing; Ru, Ge; Li, Ruixiang; Wu, Lihong; Cui, Dongqi; Yang, Pei; He, Yuwei; Wang, Jianxin

    2015-07-22

    Although several strategies have been applied for oral insulin delivery to improve insulin bioavailability, little success has been achieved. To overcome multiple barriers to oral insulin absorption simultaneously, insulin-loaded N-trimethyl chitosan chloride (TMC)-coated polylactide-co-glycoside (PLGA) nanoparticles (Ins TMC-PLGA NPs) were formulated in our study. The Ins TMC-PLGA NPs were prepared using the double-emulsion solvent evaporation method and were characterized to determine their size (247.6 ± 7.2 nm), ζ-potential (45.2 ± 4.6 mV), insulin-loading capacity (7.8 ± 0.5%) and encapsulation efficiency (47.0 ± 2.9%). The stability and insulin release of the nanoparticles in enzyme-containing simulated gastrointestinal fluids suggested that the TMC-PLGA NPs could partially protect insulin from enzymatic degradation. Compared with unmodified PLGA NPs, the positively charged TMC-PLGA NPs could improve the mucus penetration of insulin in mucus-secreting HT29-MTX cells, the cellular uptake of insulin via clathrin- or adsorption-mediated endocytosis in Caco-2 cells and the permeation of insulin across a Caco-2 cell monolayer through tight junction opening. After oral administration in mice, the TMC-PLGA NPs moved more slowly through the gastrointestinal tract compared with unmodified PLGA NPs, indicating the mucoadhesive property of the nanoparticles after TMC coating. Additionally, in pharmacological studies in diabetic rats, orally administered Ins TMC-PLGA NPs produced a stronger hypoglycemic effect, with 2-fold higher relative pharmacological availability compared with unmodified NPs. In conclusion, oral insulin absorption is improved by TMC-PLGA NPs with the multiple absorption barriers overcome simultaneously. TMC-PLGA NPs may be a promising drug delivery system for oral administration of macromolecular therapeutics.

  13. Cronobacter sakazakii clinical isolates overcome host barriers and evade the immune response.

    PubMed

    Almajed, Faisal S; Forsythe, Stephen J

    2016-01-01

    Cronobacter sakazakii is the most frequently clinically isolated species of the Cronobacter genus. However the virulence factors of C. sakazakii including their ability to overcome host barriers remains poorly studied. In this study, ten clinical isolates of C. sakazakii were assessed for their ability to invade and translocate through human colonic carcinoma epithelial cells (Caco-2) and human brain microvascular endothelial cells (HBMEC). Their ability to avoid phagocytosis in human macrophages U937 and human brain microglial cells was investigated. Additionally, they were tested for serum sensitivity and the presence of the Cronobacter plasminogen activation gene (cpa) gene, which is reported to confer serum resistance. Our data showed that the clinical C. sakazakii strains invaded and translocated through Caco-2 and HBMEC cell lines and some strains showed significantly higher levels of invasion and translocation. Moreover, C. sakazakii was able to persist and even multiply in phagocytic macrophage and microglial cells. All strains, except one, were able to withstand human serum exposure, the single serum sensitive strain was also the only one which did not encode for the cpa gene. These results demonstrate that C. sakazakii clinical isolates are able to overcome host barriers and evade the host immune response indicating their capacity to cause diseases such as necrotizing enterocolitis (NEC) and meningitis. Our data showed for the first time the ability of C. sakazakii clinical isolates to survive and multiply within human microglial cells. Additionally, it was shown that C. sakazakii clinical strains have the capacity to translocate through the Caco-2 and HBMEC cell lines paracellularly.

  14. Overcoming barriers to implementing patient-reported outcomes in an electronic health record: a case report

    PubMed Central

    Listhaus, Alyson; Covarrubias, Constanza M; Schmidt, Siegfried OF; Mackey, Sean; Carek, Peter J; Fillingim, Roger B; Hurley, Robert W

    2016-01-01

    In this case report, the authors describe the implementation of a system for collecting patient-reported outcomes and integrating results in an electronic health record. The objective was to identify lessons learned in overcoming barriers to collecting and integrating patient-reported outcomes in an electronic health record. The authors analyzed qualitative data in 42 documents collected from system development meetings, written feedback from users, and clinical observations with practice staff, providers, and patients. Guided by the Unified Theory on the Adoption and Use of Information Technology, 5 emergent themes were identified. Two barriers emerged: (i) uncertain clinical benefit and (ii) time, work flow, and effort constraints. Three facilitators emerged: (iii) process automation, (iv) usable system interfaces, and (v) collecting patient-reported outcomes for the right patient at the right time. For electronic health record-integrated patient-reported outcomes to succeed as useful clinical tools, system designers must ensure the clinical relevance of the information being collected while minimizing provider, staff, and patient burden. PMID:26159464

  15. Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy.

    PubMed

    Mastorakos, Panagiotis; da Silva, Adriana L; Chisholm, Jane; Song, Eric; Choi, Won Kyu; Boyle, Michael P; Morales, Marcelo M; Hanes, Justin; Suk, Jung Soo

    2015-07-14

    Gene therapy has emerged as an alternative for the treatment of diseases refractory to conventional therapeutics. Synthetic nanoparticle-based gene delivery systems offer highly tunable platforms for the delivery of therapeutic genes. However, the inability to achieve sustained, high-level transgene expression in vivo presents a significant hurdle. The respiratory system, although readily accessible, remains a challenging target, as effective gene therapy mandates colloidal stability in physiological fluids and the ability to overcome biological barriers found in the lung. We formulated highly stable DNA nanoparticles based on state-of-the-art biodegradable polymers, poly(β-amino esters) (PBAEs), possessing a dense corona of polyethylene glycol. We found that these nanoparticles efficiently penetrated the nanoporous and highly adhesive human mucus gel layer that constitutes a primary barrier to reaching the underlying epithelium. We also discovered that these PBAE-based mucus-penetrating DNA nanoparticles (PBAE-MPPs) provided uniform and high-level transgene expression throughout the mouse lungs, superior to several gold standard gene delivery systems. PBAE-MPPs achieved robust transgene expression over at least 4 mo following a single administration, and their transfection efficiency was not attenuated by repeated administrations, underscoring their clinical relevance. Importantly, PBAE-MPPs demonstrated a favorable safety profile with no signs of toxicity following intratracheal administration.

  16. Creating sustainable local health information exchanges: can barriers to stakeholder participation be overcome?

    PubMed

    Grossman, Joy M; Kushner, Kathryn L; November, Elizabeth A

    2008-02-01

    Local health information exchanges (HIEs) hold the promise of collecting patient clinical data across sites of care to provide more complete and timely information for treatment, as well as supporting quality improvement and reporting, public health activities, and clinical research. Findings from a study of stakeholder perspectives on participation in four HIEs by the Center for Studying Health System Change (HSC) and the National Institute for Health Care Management (NIHCM) Foundation suggest, however, that barriers to achieving data exchange remain high. Concerns about loss of competitive advantage and data misuse impede provider and health plan willingness to contribute patient data. Additionally, uncertainty about who benefits from HIEs is affecting stakeholder willingness to fund the exchanges. The more mature exchanges--Cincinnati-based HealthBridge and the Indiana Health Information Exchange (IHIE)--have achieved some viability by meeting a specific business need--more efficient delivery of hospital test results to physicians. The newer exchanges--CareSpark, serving northeast Tennessee and southwest Virginia, and the Tampa Bay Regional Health Information Organization (RHIO)--have struggled to identify and finance initial services without a similar critical mass of hospital participation. While narrow data exchange efforts that improve transaction efficiency may be a pragmatic first step to overcome barriers to stakeholder participation, expanding HIEs to achieve the broad-based data exchange necessary for quality reporting and pay-for-performance (P4P) activities raises more challenges.

  17. Electrical, magnetic, photomechanical and cavitational waves to overcome skin barrier for transdermal drug delivery.

    PubMed

    Wong, Tin Wui

    2014-11-10

    Transdermal drug delivery is hindered by the barrier property of the stratum corneum. It limits the route to transport of drugs with a log octanol-water partition coefficient of 1 to 3, molecular weight of less than 500Da and melting point of less than 200°C. Active methods such as iontophoresis, electroporation, sonophoresis, magnetophoresis and laser techniques have been investigated for the past decades on their ability, mechanisms and limitations in modifying the skin microenvironment to promote drug diffusion and partition. Microwave, an electromagnetic wave characterized by frequencies range between 300MHz and 300GHz, has recently been reported as the potential skin permeation enhancer. Microwave has received a widespread application in food, engineering and medical sectors. Its potential use to facilitate transdermal drug transport is still in its infancy stage of evaluation. This review provides an overview and update on active methods utilizing electrical, magnetic, photomechanical and cavitational waves to overcome the skin barrier for transdermal drug administration with insights into mechanisms and future perspectives of the latest microwave technique described.

  18. Overcoming Barriers in Kidney Health-Forging a Platform for Innovation.

    PubMed

    Linde, Peter G; Archdeacon, Patrick; Breyer, Matthew D; Ibrahim, Tod; Inrig, Jula K; Kewalramani, Reshma; Lee, Celeste Castillo; Neuland, Carolyn Y; Roy-Chaudhury, Prabir; Sloand, James A; Meyer, Rachel; Smith, Kimberly A; Snook, Jennifer; West, Melissa; Falk, Ronald J

    2016-07-01

    Innovation in kidney diseases is not commensurate with the effect of these diseases on human health and mortality or innovation in other key therapeutic areas. A primary cause of the dearth in innovation is that kidney diseases disproportionately affect a demographic that is largely disenfranchised, lacking sufficient advocacy, public attention, and funding. A secondary and likely consequent cause is that the existing infrastructure supporting nephrology research pales in comparison with those for other internal medicine specialties, especially cardiology and oncology. Citing such inequities, however, is not enough. Changing the status quo will require a coordinated effort to identify and redress the existing deficits. Specifically, these deficits relate to the need to further develop and improve the following: understanding of the disease mechanisms and pathophysiology, patient engagement and activism, clinical trial infrastructure, and investigational clinical trial designs as well as coordinated efforts among critical stakeholders. This paper identifies potential solutions to these barriers, some of which are already underway through the Kidney Health Initiative. The Kidney Health Initiative is unique and will serve as a current and future platform from which to overcome these barriers to innovation in nephrology.

  19. Overcoming barriers to implementing patient-reported outcomes in an electronic health record: a case report.

    PubMed

    Harle, Christopher A; Listhaus, Alyson; Covarrubias, Constanza M; Schmidt, Siegfried Of; Mackey, Sean; Carek, Peter J; Fillingim, Roger B; Hurley, Robert W

    2016-01-01

    In this case report, the authors describe the implementation of a system for collecting patient-reported outcomes and integrating results in an electronic health record. The objective was to identify lessons learned in overcoming barriers to collecting and integrating patient-reported outcomes in an electronic health record. The authors analyzed qualitative data in 42 documents collected from system development meetings, written feedback from users, and clinical observations with practice staff, providers, and patients. Guided by the Unified Theory on the Adoption and Use of Information Technology, 5 emergent themes were identified. Two barriers emerged: (i) uncertain clinical benefit and (ii) time, work flow, and effort constraints. Three facilitators emerged: (iii) process automation, (iv) usable system interfaces, and (v) collecting patient-reported outcomes for the right patient at the right time. For electronic health record-integrated patient-reported outcomes to succeed as useful clinical tools, system designers must ensure the clinical relevance of the information being collected while minimizing provider, staff, and patient burden.

  20. Understanding and Overcoming Barriers to Upper Limb Surgical Reconstruction After Tetraplegia: The Need for Interdisciplinary Collaboration.

    PubMed

    Punj, Vandana; Curtin, Catherine

    2016-06-01

    There are approximately 300,000 persons with spinal cord injury living in the United States, and nearly 60% of these persons have suffered tetraplegia with resultant alterations in body function, activity, and therefore participation. Restoring hand function can improve independence, and various studies have shown that persons with tetraplegia rate restoration of arm and hand function higher than bowel and bladder control, walking, or sexuality. There are conservative options to improve upper limb function in this population (eg, orthoses, neuroprostheses). Surgical interventions are also available, and 70% of surgical patients report satisfaction and improvement in various activities of daily living after surgery to restore arm and hand function. Despite these positive surgical outcomes, <10% of the eligible population of 60% to 70% undergo tendon transfer surgery to restore function. Underutilization of surgical interventions can be explained by population-, provider-, and health care systems-specific barriers. With further education of providers and patients and team building across disciplines these barriers can be overcome, ultimately leading to reduced disability and improved quality of life for persons with tetraplegia.

  1. Evidence for Health II: Overcoming barriers to using evidence in policy and practice.

    PubMed

    Andermann, Anne; Pang, Tikki; Newton, John N; Davis, Adrian; Panisset, Ulysses

    2016-03-14

    Even the highest quality evidence will have little impact unless it is incorporated into decision-making for health. It is therefore critical to overcome the many barriers to using evidence in decision-making, including (1) missing the window of opportunity, (2) knowledge gaps and uncertainty, (3) controversy, irrelevant and conflicting evidence, as well as (4) vested interests and conflicts of interest. While this is certainly not a comprehensive list, it covers a number of main themes discussed in the knowledge translation literature on this topic, and better understanding these barriers can help readers of the evidence to be more savvy knowledge users and help researchers overcome challenges to getting their evidence into practice. Thus, the first step in being able to use research evidence for improving population health is ensuring that the evidence is available at the right time and in the right format and language so that knowledge users can take the evidence into consideration alongside a multitude of other factors that also influence decision-making. The sheer volume of scientific publications makes it difficult to find the evidence that can actually help inform decisions for health. Policymakers, especially in low- and middle-income countries, require context-specific evidence to ensure local relevance. Knowledge synthesis and dissemination of policy-relevant local evidence is important, but it is still not enough. There are times when the interpretation of the evidence leads to various controversies and disagreements, which act as barriers to the uptake of evidence. Research evidence can also be influenced and misused for various aims and agendas. It is therefore important to ensure that any new evidence comes from reliable sources and is interpreted in light of the overall body of scientific literature. It is not enough to simply produce evidence, nor even to synthesize and package evidence into a more user-friendly format. Particularly at the policy

  2. Overcoming Access Barriers for Facility-based Delivery in Low-income Settings: Insights from Bangladesh and Uganda

    PubMed Central

    Rahman, Syed Azizur; Ssengooba, Freddie

    2006-01-01

    Women in both Bangladesh and Uganda face a number of barriers to delivery in professional health facilities, including costs, transportation problems, and sociocultural norms to deliver at home. Some women in both the countries manage to overcome these barriers. This paper reports on a comparative qualitative study investigating how some women and their families were able to use professional delivery services. The study provides insights into the decision-making processes and overcoming access barriers. Husbands were found to be particularly important in Uganda, while, in Bangladesh, a number of individuals could influence care-seeking, including unqualified local healers or traditional birth attendants. In both the settings, cost and transport barriers were often overcome through social networks. Social prohibitions on birth in the health facility did not feature strongly in women's accounts, with several Ugandan women explaining that friends or peers also used facilities, while, in Bangladesh, perceived complications apparently justified the use of professional medical care. Investigating the ways in which some women can overcome common barriers can help inform policy and planning to increase the use of health facilities for child delivery. PMID:17591340

  3. Let's not contribute to disparities: the best methods for teaching clinicians how to overcome language barriers to health care.

    PubMed

    Diamond, Lisa C; Jacobs, Elizabeth A

    2010-05-01

    Clinicians should be educated about how language barriers contribute to disparities for patients with limited English proficiency (LEP). However, educators must avoid developing educational interventions that increase health disparities for LEP patients. For example, studies suggest that teaching "Medical Spanish" or related courses may actually contribute to health care disparities if clinicians begin using these non-English language skills inappropriately with patients. We discuss the risks and benefits of teaching specific cultural competence skills and make evidence-based recommendations for the teaching content and methods for educational interventions focused on overcoming language barriers in health care. At minimum, we suggest such interventions include: (1) the role of language barriers in health disparities, (2) means of overcoming language barriers, (3) how to work with interpreters, (4) identifying and fixing problems in interpreted encounters, and (5) appropriate and safe use of one's own limited non-English language skills.

  4. Reassortment and mutation of the avian influenza virus polymerase PA subunit overcome species barriers.

    PubMed

    Mehle, Andrew; Dugan, Vivien G; Taubenberger, Jeffery K; Doudna, Jennifer A

    2012-02-01

    The emergence of new pandemic influenza A viruses requires overcoming barriers to cross-species transmission as viruses move from animal reservoirs into humans. This complicated process is driven by both individual gene mutations and genome reassortments. The viral polymerase complex, composed of the proteins PB1, PB2, and PA, is a major factor controlling host adaptation, and reassortment events involving polymerase gene segments occurred with past pandemic viruses. Here we investigate the ability of polymerase reassortment to restore the activity of an avian influenza virus polymerase that is normally impaired in human cells. Our data show that the substitution of human-origin PA subunits into an avian influenza virus polymerase alleviates restriction in human cells and increases polymerase activity in vitro. Reassortants with 2009 pandemic H1N1 PA proteins were the most active. Mutational analyses demonstrated that the majority of the enhancing activity in human PA results from a threonine-to-serine change at residue 552. Reassortant viruses with avian polymerases and human PA subunits, or simply the T552S mutation, displayed faster replication kinetics in culture and increased pathogenicity in mice compared to those containing a wholly avian polymerase complex. Thus, the acquisition of a human PA subunit, or the signature T552S mutation, is a potential mechanism to overcome the species-specific restriction of avian polymerases and increase virus replication. Our data suggest that the human, avian, swine, and 2009 H1N1-like viruses that are currently cocirculating in pig populations set the stage for PA reassortments with the potential to generate novel viruses that could possess expanded tropism and enhanced pathogenicity.

  5. Overcoming barriers to hepatitis B immunisation by a dedicated hepatitis B immunisation service

    PubMed Central

    Larcher, V; Bourne, J; Aitken, C; Jeffries, D; Hodes, D; SLOAN, D.; RAMSAY, M.; GOLDBERG, D.; BRAMLEY, C.

    2001-01-01

    AIMS—To determine the effectiveness of a selective hospital based hepatitis B immunisation programme and the barriers to be overcome in obtaining a successful outcome.
METHODS—Retrospective case note review of 265 infants born over a five year period to hepatitis B carrier mothers at a university affiliated hospital in Hackney, London.
RESULTS—A total of 242 infants (91%) were fully vaccinated; 217 (82%) had serology; 31 required booster doses. Percentages failing to reach second, third vaccinations, and serology on schedule rose exponentially (7%, 18%, 33% respectively). Mobility was high (25%) and significantly affected outcome. A total of 95% Hackney resident babies were fully vaccinated compared with 78% non-residents. Uptake of routine immunisations was higher in Hackney residents than non-residents and greater in those who were eligible for hepatitis B vaccine. Name changes occurred in 35%. Translation requirements were high (85% for Turkish, Vietnamese, and Asian families). Requirements for specific postnatal counselling of mothers and hepatology referral fell significantly during the course of the study. Only seven of 22 babies born in 1995 in Tower Hamlets compared with 53 of 58 Hackney babies received a full vaccination course in non-hospital based primary care.
CONCLUSION—In inner city areas with high prevalence of hepatitis B carriage, mobility, and diverse ethnicity, a dedicated centralised immunisation service can be highly effective, provided that adequate support services (translation, counselling, and parental referral) are available.
 PMID:11159283

  6. Lung Gene Therapy with Highly Compacted DNA Nanoparticles that Overcome the Mucus Barrier

    PubMed Central

    Suk, Jung Soo; Kim, Anthony J.; Trehan, Kanika; Schneider, Craig S.; Cebotaru, Liudmila; Woodward, Owen M.; Boylan, Nicholas J.; Boyle, Michael P.; Lai, Samuel K.; Guggino, William B.; Hanes, Justin

    2014-01-01

    Inhaled gene carriers must penetrate the highly viscoelastic and adhesive mucus barrier in the airway in order to overcome rapid mucociliary clearance and reach the underlying epithelium; however, even the most widely used viral gene carriers are unable to efficiently do so. We developed two polymeric gene carriers that compact plasmid DNA into small and highly stable nanoparticles with dense polyethylene glycol (PEG) surface coatings. These highly compacted, densely PEG-coated DNA nanoparticles rapidly penetrate human cystic fibrosis (CF) mucus ex vivo and mouse airway mucus ex situ. Intranasal administration of the mucus penetrating DNA nanoparticles greatly enhanced particle distribution, retention and gene transfer in the mouse lung airways compared to conventional gene carriers. Successful delivery of a full-length plasmid encoding the cystic fibrosis transmembrane conductance regulator protein was achieved in mouse lungs and airway cells, including a primary culture of mucus-covered human airway epithelium grown at air-liquid interface, without causing acute inflammation or toxicity. Highly compacted mucus penetrating DNA nanoparticles hold promise for lung gene therapy. PMID:24440664

  7. Overcoming Barriers; Enabling Learners: Planning, Designing and Delivering the Full-Time FE Curriculum in Scotland's Colleges

    ERIC Educational Resources Information Center

    Her Majesty's Inspectorate of Education, 2006

    2006-01-01

    The further education (FE) curriculum in Scotland's colleges aims to enable people to develop skills and capacities which will improve the quality of their working, personal, family and community life. To achieve this aim people need assistance to overcome barriers constraining their confidence and ability to take part in learning situations and…

  8. Helping Our Most Vulnerable Families Overcome Barriers to Work and Achieve Financial Success. KIDS COUNT 2005 Essay

    ERIC Educational Resources Information Center

    Annie E. Casey Foundation, 2005

    2005-01-01

    This essay, taken from the 2005 KIDS COUNT Data Book, examines four employment barriers that policymakers and others consider among the most difficult to overcome: substance abuse, domestic violence, a history of incarceration, and depression. These burdens can diminish a person's motivation and ability to find work. Furthermore, they can make it…

  9. All Health Plans Need CLAMS: Culturally and Linguistically Appropriate Materials for Diverse Populations Can Overcome Language Barriers to Effective Treatment.

    ERIC Educational Resources Information Center

    Smith, Sandra; Gonzales, Virginia

    2000-01-01

    CLAMs are "Culturally and Linguistically Appropriate Materials" designed for diverse populations to help them overcome language barriers to effective treatment. The demographic shift underway in the United States is making the country more linguistically diverse. Health plans need to accommodate this shift, because without information patients…

  10. Overcoming Relationship-Initiation Barriers: The Impact of a Computer-Dating System on Sex Role, Shyness, and Appearance Inhibitions.

    ERIC Educational Resources Information Center

    Scharlott, Bradford W.; Christ, William G.

    1995-01-01

    A survey of the users of an online computer-mediated matchmaking service showed that their communication patterns and objectives varied by their sex, shyness level, and appearance. Intrinsic aspects of this system helped some users overcome relationship-initiation barriers rooted in sex role, shyness, and appearance inhibitions. (Author)

  11. Translating Research to Practice: Overcoming Barriers to Implementing Effective Off-Campus Party Intervention. Issues in Prevention

    ERIC Educational Resources Information Center

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2012

    2012-01-01

    This issue of "Issues in Prevention" focuses on overcoming barriers in implementing effective off-campus party intervention. This issue contains the following articles: (1) Confronting the Problems Associated With Off-Campus Parties With Evidence-Based Strategies (John D. Clapp); (2) Overview of Research on Effective Off-Campus Party…

  12. Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye - Part I - Barriers and determining factors in ocular delivery.

    PubMed

    Sánchez-López, E; Espina, M; Doktorovova, S; Souto, E B; García, M L

    2017-01-01

    Ocular drug delivery is still a challenge for researchers in the field of pharmaceutical technology due to anatomical and physiological eye characteristics. The tissue barriers (such as cornea, conjunctiva, blood aqueous barrier, and blood-retinal barrier) limit the access of drugs to their targets. Taking into account the short retention time in the precorneal area of classical ocular dosage forms (e.g. solutions, suspensions or ointments) which are rapidly eliminated by tears and eyelid movement, only less than five percent of the administered drug attains intraocular structures. With the aim to overcome ocular barriers, drug delivery systems, able to increase ocular bioavailability reducing side effects, are recognized as promising alternative. In this review, the main barriers and strategies to increase drug transport in ocular delivery are comprehensively discussed, highlighting the factors involved in ocular transport of SLN and NLC.

  13. Nanoparticles decorated with proteolytic enzymes, a promising strategy to overcome the mucus barrier.

    PubMed

    Pereira de Sousa, Irene; Cattoz, Beatrice; Wilcox, Matthew D; Griffiths, Peter C; Dalgliesh, Robert; Rogers, Sarah; Bernkop-Schnürch, Andreas

    2015-11-01

    The intestinal mucus gel layer represents a stumbling block for drug adsorption. This study is aimed to formulate a nanoparticulate system able to overcome this barrier by cleaving locally the glycoprotein substructures of the mucus. Mucolytic enzymes such as papain (PAP) and bromelain (BRO) were covalently conjugated to poly(acrylic acid) (PAA). Nanoparticles (NPs) were then formulated via ionic gelation method and characterized by particle size, zeta potential, enzyme content and enzymatic activity. The NPs permeation quantified by rotating tube studies was correlated with changes in the mucus gel layer structure determined by pulsed-gradient-spin-echo NMR (PGSE-NMR), small-angle neutron scattering (SANS) and spin-echo SANS (SESANS). PAP and BRO functionalized NPs had an average size in the range of 250 and 285 nm and a zeta potential that ranged between -6 and -5 mV. The enzyme content was 242 μg enzyme/mg for PAP modified NPs and 253 μg enzyme/mg for BRO modified NPs. The maintained enzymatic activity was 43% for PAP decorated NPs and 76% for BRO decorated NPs. The rotating tube technique revealed a better performance of BRO decorated NPs compared to PAA decorated NPs, with a 4.8-fold higher concentration of NPs in the inner slice of mucus. Addition of 0.5 wt% of enzyme functionalized NPs to 5 wt% intestinal mucin led to c.a. 2-fold increase in the mobility of the mucin as measured by PGSE-NMR indicative of a significant break-up of the structure of the mucin. SANS and SESANS measurements further revealed a change in structure of the intestinal mucus induced by the incorporation of the functionalized NPs mostly occurring at a length scale longer than 0.5 μm. Accordingly, BRO decorated NPs show higher potential than PAP functionalized NPs as mucus permeating drug delivery systems.

  14. Overcoming the blood-brain tumor barrier for effective glioblastoma treatment.

    PubMed

    van Tellingen, O; Yetkin-Arik, B; de Gooijer, M C; Wesseling, P; Wurdinger, T; de Vries, H E

    2015-03-01

    demonstrate 'within-organ-metastasis' away from the core part to brain areas displaying a more organized and less leaky BBTB. Hence, drug delivery in glioblastoma deserves explicit attention as otherwise new experimental therapies will continue to fail. In the current review we highlight different aspects of the BBTB in glioma patients and preclinical models and discuss the advantages and drawbacks of drug delivery approaches for the treatment of glioma patients. We provide an overview on methods to overcome the BBTB, including osmotic blood-brain barrier disruption (BBBD), bradykinin receptor-mediated BBTB opening, inhibition of multidrug efflux transporters, receptor-mediated transport systems and physiological circumvention of the BBTB. While our knowledge about the molecular biology of glioma cells is rapidly expanding and is, to some extent, already assisting us in the design of tumor-tailored therapeutics, we are still struggling to develop modalities to expose the entire tumor to such therapeutics at pharmacologically meaningful quantities. Therefore, we must expand our knowledge about the fundamentals of the BBTB as a step toward the design of practical and safe devices and approaches for enhanced drug delivery into the diseased brain area.

  15. Overcoming hybridization barriers by the secretion of the maize pollen tube attractant ZmEA1 from Arabidopsis ovules.

    PubMed

    Márton, Mihaela L; Fastner, Astrid; Uebler, Susanne; Dresselhaus, Thomas

    2012-07-10

    A major goal of plant reproduction research is to understand and overcome hybridization barriers so that the gene pool of crop plants can be increased and improved upon. After successful pollen germination on a receptive stigma, the nonmotile sperm cells of flowering plants are transported via the pollen tube (PT) to the egg apparatus for the achievement of double fertilization. The PT path is controlled by various hybridization mechanisms probably involving a larger number of species-specific molecular interactions. The egg-apparatus-secreted polymorphic peptides ZmEA1 in maize and LURE1 and LURE2 in Torenia fournieri as well as TcCRP1 in T. concolor were shown to be required for micropylar PT guidance, the last step of the PT journey. We report here that ZmEA1 attracts maize PTs in vitro and arrests their growth at higher concentrations. Furthermore, it binds to the subapical region of maize PT tips in a species-preferential manner. To overcome hybridization barriers at the level of gametophytic PT guidance, we expressed ZmEA1 in Arabidopsis synergid cells. Secreted ZmEA1 enabled Arabidopsis ovules to guide maize PT in vitro in a species-preferential manner to the micropylar opening of the ovule. These results demonstrate that the egg-apparatus-controlled reproductive-isolation barrier of PT guidance can be overcome even between unrelated plant families.

  16. Simulations and Games: Overcoming the Barriers to Their Use in Higher Education

    ERIC Educational Resources Information Center

    Moizer, Jonathan; Lean, Jonathan; Towler, Michael; Abbey, Caroline

    2009-01-01

    Based on a categorization of simulation and gaming barriers developed in a previous study, this work seeks to explore in greater depth the composition and nature of these obstacles. It examines the interrelationships between the barriers and the impact of other contextual factors in the pedagogic environment. A series of in-depth interviews were…

  17. Energy management action plan: Developing a strategy for overcoming institutional barriers to municipal energy conservation

    SciTech Connect

    Not Available

    1992-12-31

    Energy offices working to improve efficiency of local government facilities face not only technical tasks, but institutional barriers, such as budget structures that do not reward efficiency, a low awareness of energy issues, and purchasing procedures based only on minimizing initial cost. The bureau, in working to remove such barriers in San Francisco, has identified 37 institutional barriers in areas such as operations & maintenance, purchasing, and facility design; these barriers were then reorganized into three groupings-- policy & attitudes, budget & incentives, and awareness & information-- and mapped. This map shows that the barriers mutually reinforce each other, and that a holistic approach is required for permanent change. The city`s recreation & parks department was used as a model department, and information about facility energy use was compiled into a departmental energy review. Staff interviews showed how barriers affect conservation. The bureau then generated ideas for projects to remove specific barriers and rated them according to potential impact and the resources required to implement them. Four of the six projects selected focused on maintenance staff: a cost- sharing lighting retrofit program, a boiler efficiency program, a departmental energy tracking system, and a budgetary incentive program for conservation. The other two projects are city-wide: promotion of a new term contract supplying energy-efficient light materials, and publication/distribution of ENERGY NEWS newsletter. A general methodology, the EMAP Strategy Guide, has been created to assist other energy offices in developing EMAPs.

  18. A review of multifunctional nanoemulsion systems to overcome oral and CNS drug delivery barriers.

    PubMed

    Ganta, Srinivas; Deshpande, Dipti; Korde, Anisha; Amiji, Mansoor

    2010-10-01

    The oral and central nervous systems (CNS) present a unique set of barriers to the delivery of important diagnostic and therapeutic agents. Extensive research over the past few years has enabled a better understanding of these physical and biological barriers based on tight cellular junctions and expression of active transporters and metabolizing enzymes at the luminal surfaces of the gastrointestinal (GI) tract and the blood-brain barrier (BBB). This review focuses on the recent understanding of transport across the GI tract and BBB and the development of nanotechnology-based delivery strategies that can enhance bioavailability of drugs. Multifunctional lipid nanosystems, such as oil-in-water nanoemulsions, that integrate enhancement in permeability, tissue and cell targeting, imaging, and therapeutic functions are especially promising. Based on strategic choice of edible oils, surfactants and additional surface modifiers, and different types of payloads, rationale design of multifunctional nanoemulsions can serve as a safe and effective delivery vehicle across oral and CNS barriers.

  19. Tailored interventions to overcome identified barriers to change: effects on professional practice and health care outcomes

    PubMed Central

    Baker, Richard; Camosso-Stefinovic, Janette; Gillies, Clare; Shaw, Elizabeth J; Cheater, Francine; Flottorp, Signe; Robertson, Noelle

    2014-01-01

    Background In the previous version of this review, the effectiveness of interventions tailored to barriers to change was found to be uncertain. Objectives To assess the effectiveness of interventions tailored to address identified barriers to change on professional practice or patient outcomes. Search methods For this update, in addition to the EPOC Register and pending files, we searched the following databases without language restrictions, from inception until August 2007: MEDLINE, EMBASE, CINAHL, BNI and HMIC. We searched the National Research Register to November 2007. We undertook further searches to October 2009 to identify potentially eligible published or ongoing trials. Selection criteria Randomised controlled trials (RCTs) of interventions tailored to address prospectively identified barriers to change that reported objectively measured professional practice or healthcare outcomes in which at least one group received an intervention designed to address prospectively identified barriers to change. Data collection and analysis Two reviewers independently assessed quality and extracted data. We undertook quantitative and qualitative analyses. The quantitative analyses had two elements. We carried out a meta-regression to compare interventions tailored to address identified barriers to change with either no interventions or an intervention(s) not tailored to the barriers.We carried out heterogeneity analyses to investigate sources of differences in the effectiveness of interventions. These included the effects of: risk of bias, concealment of allocation, rigour of barrier analysis, use of theory, complexity of interventions, and the reported presence of administrative constraints. Main results We included 26 studies comparing an intervention tailored to address identified barriers to change to no intervention or an intervention(s) not tailored to the barriers. The effect sizes of these studies varied both across and within studies. Twelve studies provided

  20. Ground-Source Heat Pumps. Overview of Market Status, Barriers to Adoption, and Options for Overcoming Barriers

    SciTech Connect

    Goetzler, William; Zogg, Robert; Lisle, Heather; Burgos, Javier

    2009-02-03

    February 2009 final report submitted to DOE by Navigant Consulting, Inc. This report summarizes the status of ground-source heat pump (GSHP) technology and market penetration globally, estimates the energy saving potential of GSHPs in the U.S., identifies key market barriers that are inhibiting wider market adoption of GSHPs, and recommends initiatives that can be implemented or facilitated by the DOE to accelerate market adoption.

  1. Barriers that practitioners face when initiating insulin therapy in general practice settings and how they can be overcome

    PubMed Central

    Bin rsheed, Abdulaziz; Chenoweth, Ian

    2017-01-01

    AIM To explore primary care physicians’ perspectives on possible barriers to the use of insulin. METHODS This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight electronic databases were searched (between January 1, 1994 and August 31, 2014) for relevant studies. A search for grey literature and a review of the references in the retrieved studies were also conducted. Studies that focused on healthcare providers’ perspectives on possible barriers to insulin initiation with type 2 diabetic patients were included, as well as articles suggesting solutions for these barriers. Review articles and studies that only considered patients’ perspectives were excluded. RESULTS A total of 19 studies met the inclusion criteria and were therefore included in this study: 10 of these studies used qualitative methods, 8 used quantitative methods and 1 used mixed methods. Studies included a range of different health care settings. The findings are reported under four broad categories: The perceptions of primary care physicians about the barriers to initiate insulin therapy for type 2 diabetes patients, how primary care physicians assess patients prior to initiating insulin, professional roles and possible solutions to overcome these barriers. The barriers described were many and covered doctor, patient, system and technological aspects. Interventions that focused on doctor training and support, or IT-based decision support were few, and did not result in significant improvement. CONCLUSION Primary care physicians’ known delay in insulin initiation is multifactorial. Published reports of attempts to find solutions for these barriers were limited in number. PMID:28138362

  2. Overcoming the barrier of narrative adherence in conflicts through awareness of the psychological bias of naïve realism.

    PubMed

    Nasie, Meytal; Bar-Tal, Daniel; Pliskin, Ruthie; Nahhas, Eman; Halperin, Eran

    2014-11-01

    One significant socio-psychological barrier for peaceful resolution of conflicts is each party's adherence to its own collective narrative. We hypothesized that raising awareness to the psychological bias of naïve realism and its identification in oneself would provide a path to overcoming this barrier, thus increasing openness to the adversary's narrative. We conducted three experimental studies in the context of the Israeli-Palestinian conflict. Studies 1 and 2, conducted among Jewish Israelis and Palestinian Israelis, respectively, revealed that participants with hawkish political ideology reported greater openness to the adversary's narrative when they were made aware of naïve realism bias. Study 3 revealed that hawkish participants at the baseline adhered to the ingroup narrative and resisted the adversary's narrative more than dovish participants. They were also more able to identify the bias in themselves upon learning about it. This identification may explain why the manipulation led to bias correction only among hawkish participants.

  3. Strategies for Overcoming Barriers to Training and Education for Canadians with Disabilities. Lessons in Learning

    ERIC Educational Resources Information Center

    Canadian Council on Learning, 2009

    2009-01-01

    If stronger skills and more education are key to greater labour force participation, then it is important to identify critical barriers to education and training for Canadians with disabilities. In 2008, the Canadian Council on Learning's Adult Learning Knowledge Centre funded a "Community Outreach Initiative for Learner's with…

  4. Supporting Instructors in Overcoming Self-Efficacy and Background Barriers to Adoption

    ERIC Educational Resources Information Center

    Reid, Pat

    2017-01-01

    Most academic technology areas of higher education institutes do not feel faculty technology adoption is adequate (Hartman (EDUCAUSE Rev 43(6), 2008)). Among the barriers to instructional technology adoption are faculty self-efficacy and background. Self-efficacy encompasses the faculty member's belief or confidence in his ability to succeed.…

  5. Designing Caregiver-Implemented Shared-Reading Interventions to Overcome Implementation Barriers

    ERIC Educational Resources Information Center

    Justice, Laura M.; Logan, Jessica R.; Damschroder, Laura

    2015-01-01

    Purpose: This study presents an application of the theoretical domains framework (TDF; Michie et al., 2005), an integrative framework drawing on behavior-change theories, to speech-language pathology. Methods: A multistep procedure was used to identify barriers affecting caregivers' implementation of shared-reading interventions with their…

  6. At-Risk Students Defy the Odds: Overcoming Barriers to Educational Success.

    ERIC Educational Resources Information Center

    Aronson, Rosa

    The phenomenon of educational resilience in at-risk students involves complex questions and answers. Seven people were interviewed whose lives are chronicled in the context of surviving and achieving despite significant barriers to success in life. They encountered common hindrances arising from poverty, racial and ethnic identity, isolation,…

  7. Overcoming Barriers to the Sexual Expression of Women with Developmental Disabilities.

    ERIC Educational Resources Information Center

    Stinson, Jennifer; Christian, LeeAnn; Dotson, Lori Ann

    2002-01-01

    This article discusses barriers to sexual fulfillment faced by women with developmental disabilities, including: access to gynecological healthcare, limited choices regarding reproductive issues, lack of sex education, and prevailing negative stereotypes that affect the way women are viewed by others and the way they view themselves.…

  8. Understanding and overcoming barriers to substance abuse treatment access for people with mental retardation.

    PubMed

    Slayter, Elspeth M

    2008-01-01

    People with mental retardation have experienced increasing levels of freedom and access to community living over the past 40 years. This has included access to alcohol, illicit drugs and the potential for developing substance abuse and related problems. The manner in which people with mental retardation have handled this access has been recognized since the de institutionalization era began. Despite this recognition, documented barriers to accessing substance abuse treatment for people with mental retardation exist and there is an overarching lack of knowledge about accessible treatment approaches for this population. Policy and practice recommendations are presented for disability and rehabilitation social workers in order to better understand and combat barriers to substance abuse treatment.

  9. Overcoming Barriers to the Market Access of Biosimilars in the European Union: The Case of Biosimilar Monoclonal Antibodies

    PubMed Central

    Moorkens, Evelien; Jonker-Exler, Clara; Huys, Isabelle; Declerck, Paul; Simoens, Steven; Vulto, Arnold G.

    2016-01-01

    Background: In 2014, six of the top ten blockbuster medicines were monoclonal antibodies. This multibillion-dollar market with expiring patents is the main driver for the development of biosimilar mAbs. With the ever-increasing cost of healthcare and the economic pressure to reduce or sustain healthcare expenses, biosimilars could be instrumental in reducing costs for medication and increasing patient access to treatment. Objectives: The aim of this study is to identify and describe the barriers to market access of biosimilar mAbs in the European Union and to analyze how these barriers could be overcome. Methods: A narrative literature review was carried out using the databases PubMed, Embase, and EconLit. Studies were published in English or Dutch. Additionally, the reference list of the articles was checked for relevant studies. Articles and conference papers known to the authors were included as well. Articles were also identified by searching on the website of the Generics and Biosimilars Initiative (GaBI) journal. Results: Six barriers were identified based on available literature: The manufacturing process, the regulatory process, intellectual property rights, lack of incentive, the impossibility of substitution, and the innovator's reach. These six barriers are presented as a possible framework to study the market access of biosimilar mAbs. Based on the literature search, recommendations can be made to overcome these barriers: (i) invest initially in advanced production processes with the help of single-use technology, experience or outsourcing (ii) gain experience with the regulatory process and establish alignment between stakeholders (iii) limit patent litigation, eliminate evergreening benefits, build out further the unitary patent and unified patent litigation system within the EU (iv) create demand-side policies, disseminate objective information (v) change attitude toward biosimilar switching/substitution, starting with physician, and patient

  10. Overcoming barriers to the mobilisation of patients in an intensive care unit.

    PubMed

    Dafoe, S; Chapman, M J; Edwards, S; Stiller, K

    2015-11-01

    We conducted a quality improvement project aimed at increasing the frequency of mobilisation in our ICU. We designed a four-part quality improvement project comprising: an audit documenting the baseline frequency of mobilisation; a staff survey evaluating perceptions of the barriers to mobilisation; identification of barriers that were amenable to change and implementation of strategies to address these; and a follow-up audit to determine their effectiveness. The setting was a tertiary care, urban, public hospital ICU in South Australia. All patients admitted to the ICU during the two audit periods were included in the audits, while all permanent/semi-permanent ICU staff were eligible for inclusion in the staff survey. We found that patient- and institution-related factors had the greatest impact on the mobilisation of patients in our ICU. Barriers identified as being amenable to change included insufficient staff education about the benefits of mobilisation, poor interdisciplinary communication and lack of leadership regarding mobilisation. Various strategies were implemented to address these barriers over a three-month period. Multivariable analyses showed that three out of four mobility outcomes did not significantly change between the baseline and follow-up audits, with a significant difference in favour of the baseline audit found for the fourth mobility outcome (maximum level of mobility). We concluded that implementing relatively simple measures to improve staff education, interdisciplinary communication and leadership regarding early progressive mobilisation was ineffective at improving mobility outcomes for patients in a large tertiary-level Australian ICU. Other strategies, such as changing sedation practices and/or increasing staffing, may be required to improve mobility outcomes of these patients.

  11. Pathogen population bottlenecks and adaptive landscapes: overcoming the barriers to disease emergence.

    PubMed

    Geoghegan, Jemma L; Senior, Alistair M; Holmes, Edward C

    2016-08-31

    Emerging diseases are a major challenge to public health. Revealing the evolutionary processes that allow novel pathogens to adapt to new hosts, also the potential barriers to host adaptation, is central to understanding the drivers of disease emergence. In particular, it is unclear how the genetics and ecology of pathogens interact to shape the likelihood of successful cross-species transmission. To better understand the determinants of host adaptation and emergence, we modelled key aspects of pathogen evolutionary dynamics at both intra- and inter-host scales, using parameter values similar to those observed in influenza virus. We considered the possibility of acquiring the necessary host adaptive mutations both before ('off-the-shelf' emergence) and after ('tailor-made' emergence) a virus is transmitted from a donor to a new recipient species. Under both scenarios, population bottlenecks at inter-host transmission act as a major barrier to host adaptation, greatly limiting the number of adaptive mutations that are able to cross the species barrier. In addition, virus emergence is hindered if the fitness valley between the donor and recipient hosts is either too steep or too shallow. Overall, our results reveal where in evolutionary parameter space a virus could adapt to and become transmissible in a new species.

  12. Coping with structural disadvantage: Overcoming negative effects of perceived barriers through bonding identities.

    PubMed

    Bakouri, Mouna; Staerklé, Christian

    2015-12-01

    Members of socially disadvantaged groups often experience societal devaluation, material hardship, and restricted opportunities, especially during critical life-course transitions. In this study, we investigate whether what we term 'bonding identities', that is identities connecting the self to significant persons whether in terms of social relationships (e.g., family relations) or in terms of categorical collective identities, help individuals negotiate structural constraints on life-course opportunities. We develop and test a model according to which greater perceived barriers to one's life projects are psychologically harmful. We then test whether bonding identities function as a buffer against these stressors' negative psychological effects. Data were collected with a standardized questionnaire from pre-apprentices, apprentices, and young employees in two institutions (N = 365). Results confirm that perceiving barriers to one's life project was harmful for self-esteem. However, for participants who defined themselves in terms of bonding identities, greater perceived barriers did not decrease their perceived coping efficacy and were less harmful for their self-esteem. These findings point to the empowering role of bonding identities (and the social relationships that they imply) for disadvantaged group members.

  13. Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation

    PubMed Central

    Sun, Yujia; Nien, Chung-Yi; Chen, Kai; Liu, Hsiao-Yun; Johnston, Jeff; Zeitlinger, Julia; Rushlow, Christine

    2015-01-01

    The Drosophila genome activator Vielfaltig (Vfl), also known as Zelda (Zld), is thought to prime enhancers for activation by patterning transcription factors (TFs). Such priming is accompanied by increased chromatin accessibility, but the mechanisms by which this occurs are poorly understood. Here, we analyze the effect of Zld on genome-wide nucleosome occupancy and binding of the patterning TF Dorsal (Dl). Our results show that early enhancers are characterized by an intrinsically high nucleosome barrier. Zld tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of Zld motifs. Without Zld, Dl binding decreases at enhancers and redistributes to open regions devoid of enhancer activity. We propose that Zld primes enhancers by lowering the high nucleosome barrier just enough to assist TFs in accessing their binding motifs and promoting spatially controlled enhancer activation if the right patterning TFs are present. We envision that genome activators in general will utilize this mechanism to activate the zygotic genome in a robust and precise manner. PMID:26335633

  14. Oculocutaneous albinism: identifying and overcoming barriers to vision care in a Nigerian population.

    PubMed

    Udeh, N N; Eze, B I; Onwubiko, S N; Arinze, O C; Onwasigwe, E N; Umeh, R E

    2014-06-01

    To assess eye care service utilization, and identify access barriers in a south-eastern Nigerian albino population. The study was a population-based, cross-sectional survey conducted in Enugu state between August, 2011 and January, 2012. Using the data base of the state's Albino Foundation and tailored awareness creation, persons living with albinism were identified and recruited at two study centres. Data on participants' socio-demographics, perception of vision, visual needs, previous eye examination and or low vision assessment, use of glasses or low vision devices were collected. Reasons for non-utilisation of available vision care services were also obtained. Descriptive and comparative statistics were performed. A p < 0.05 was considered statistically significant. The participants (n = 153; males 70; females 83; sex ratio: 1:1.1) were aged 23.46 + 10.44 SD years (range 6-60 years). Most--95.4 % of the participants had no previous low vision assessment and none--0.0% had used low vision device. Of the participants, 82.4% reported previous eye examination, 33.3% had not used spectacles previously, despite the existing need. Ignorance--88.9% and poor access--8.5% were the main barriers to uptake of vision care services. In Enugu, Nigeria, there is poor awareness and low utilization of vision care services among people with albinism. The identified barriers to vision care access are amenable to awareness creation and logistic change in the provision of appropriate vision care services.

  15. AccessAbility: Overcoming Information Barriers. Proceedings from the 1987 Spring Meeting of the Nebraska Library Association, College and University Section (Omaha, Nebraska, May 29, 1987).

    ERIC Educational Resources Information Center

    Kacena, Barbara J., Ed.

    Various aspects of the theme, "AccessAbility: Overcoming Information Barriers," are considered in the conference papers collected in this document. They include: (1) "The Library Image: A Barrier to Accessibility" (Janice S. Boyer); (2) "The Educationally Disadvantaged Student: How Can the Library Help?" (Michael Poma…

  16. OVERCOMING THE METER BARRIER AND THE FORMATION OF SYSTEMS WITH TIGHTLY PACKED INNER PLANETS (STIPs)

    SciTech Connect

    Boley, A. C.; Morris, M. A.; Ford, E. B.

    2014-09-10

    We present a solution to the long outstanding meter barrier problem in planet formation theory. As solids spiral inward due to aerodynamic drag, they will enter disk regions that are characterized by high temperatures, densities, and pressures. High partial pressures of rock vapor can suppress solid evaporation, and promote collisions between partially molten solids, allowing rapid growth. This process should be ubiquitous in planet-forming disks, which may be evidenced by the abundant class of Systems with Tightly packed Inner Planets discovered by the NASA Kepler Mission.

  17. [Overcoming language barriers with telephone interpreters: first experiences at a German children's hospital].

    PubMed

    Langer, Thorsten; Wirth, Stefan

    2014-01-01

    Language barriers in the care for patients with limited German language proficiency contribute to impaired quality of care, more frequent medical errors and decreased patient satisfaction. However, professional interpreters are not systematically used in Germany. We conducted a pilot study in a German paediatric hospital to explore the demand for an interpreter by conducting a survey among parents and to test the use of telephone interpreters. Eight percent of the respondents said they were interested in interpreter support. All physicians and parents using a telephone interpreter were very satisfied with the quality and the organisation of the service.

  18. Overcoming barriers to addressing education problems with research design: a panel discussion.

    PubMed

    Yarris, Lalena M; Gruppen, Larry D; Hamstra, Stanley J; Anders Ericsson, K; Cook, David A

    2012-12-01

    A plenary panel session at the 2012 Academic Emergency Medicine consensus conference "Education Research in Emergency Medicine: Opportunities, Challenges, and Strategies for Success" discussed barriers educators face in imagining, designing, and implementing studies to address educational challenges. This proceedings article presents a general approach to getting started in education research. Four examples of studies from the medical education literature that illustrate a distinct way to approach specific research questions are discussed. The study designs used are applicable to a variety of education research problems in emergency medicine (EM). Potential applications of studies are discussed, as well as effects and lessons learned.

  19. Overcoming Workplace Barriers: A Focus Group Study Exploring African American Mothers' Needs for Workplace Breastfeeding Support

    PubMed Central

    Johnson, Angela Marie; Kirk, Rosalind; Muzik, Maria

    2015-01-01

    Background Persistent racial disparities in breastfeeding show that African American women breastfeed at the lowest rates. Return to work is a critical breastfeeding barrier for African American women who return to work sooner than other ethnic groups and more often encounter unsupportive work environments. They also face psychosocial burdens that make breastfeeding at work uniquely challenging. Participants share personal struggles with combining paid employment and breastfeeding and suggest workplace and personal support strategies that they believe will help continue breastfeeding after a return to work. Objective To explore current perspectives on ways to support African American mothers' workplace breastfeeding behavior. Methods Pregnant African American women (n = 8), African American mothers of infants (n = 21), and lactation support providers (n = 9) participated in 1 of 6 focus groups in the Greater Detroit area. Each focus group audiotape was transcribed verbatim. Thematic analysis was used to inductively analyze focus group transcripts and field notes. Focus groups explored thoughts, perceptions, and behavior on interventions to support African American women's breastfeeding. Results Participants indicate that they generally believed breastfeeding was a healthy option for the baby; however, paid employment is a critical barrier to successful breastfeeding for which mothers receive little help. Participants felt breastfeeding interventions that support working African American mothers should include education and training for health care professionals, regulation and enforcement of workplace breastfeeding support policies, and support from peers who act as breastfeeding role models. Conclusion Culturally appropriate interventions are needed to support breastfeeding among working African American women. PMID:25714345

  20. Overcoming research barriers in Chagas disease-designing effective implementation science.

    PubMed

    Henao-Martínez, Andrés F; Colborn, Kathryn; Parra-Henao, Gabriel

    2017-01-01

    Chagas disease is a complex tropical parasitic infection. It affects a significant portion of the population in Latin America, especially in areas of poverty and poor access to health care. It also affects immigrants in high-income countries who lack access to health care due to their legal status. Millions of people are at risk of contracting the disease, and approximately 30 % of chronically infected patients will develop cardiomyopathy. The cost of caring for patients that have been infected is substantial. Basic science research has introduced new concepts and knowledge for the parasite and vector biology as well as better understanding of the pathophysiology of the disease. These research findings nevertheless require effective and timely translation into clinical practice. Likewise, the design of new research projects should account for the multiple system-based barriers. Implementation science facilitates the applicability of research findings and identifies barriers to its execution. Creation of implementation science measures to reach and sustain research programs with greater potential to impact Chagas disease are lacking. This point of view proposes opportunities for implementation science in Chagas disease and strategies for researching effective interventions for preventing and treating the disease.

  1. Microneedles and other physical methods for overcoming the stratum corneum barrier for cutaneous gene therapy.

    PubMed

    Coulman, Sion; Allender, Chris; Birchall, James

    2006-01-01

    The outermost layer of skin, the epidermis, has developed formidable physical and immunological barrier properties that prevent infiltration of deleterious chemicals and pathogens. Consequently, transdermal delivery of medicaments is currently restricted to a limited number of low molecular weight drugs. As a corollary, there has been significant recent interest in providing strategies that disrupt or circumvent the principal physical barrier, the stratum corneum, for the efficient cutaneous delivery of macromolecular and nucleic acid based therapeutics. These strategies include: electrical methods, intradermal injection, follicular delivery, particle acceleration, laser ablation, radiofrequency ablation, microscission, and microneedles. The application of microfabricated microneedle arrays to skin creates transient pathways to enable transcutaneous delivery of drugs and macromolecules. Microneedle use is simple, pain-free, and causes no bleeding, with further advantages of convenient manufacture, distribution, and disposal. To date, microneedles have been shown to deliver drug, peptide, antigen, and DNA efficiently through skin. Robust and efficient microneedle designs and compositions can be inserted into the skin without fracture. Further progress in microneedle array design, microneedle application apparatus, and integrated formulation will confirm this methodology as a realistic clinical strategy for delivering a range of medicaments, including DNA, to and through skin.

  2. Overcoming barriers to glycemic control in African Americans with type-2 diabetes: benefits of insulin therapy.

    PubMed Central

    Marshall, Merville C.

    2007-01-01

    A disproportionate number of African-American men and women are affected by obesity and diabetes. The documented rate of poor glycemic control in the African-American population may contribute to the high rate of morbidity and mortality due to diabetes observed in these patients. Since the benefits of strict glycemic control have been demonstrated in multiple large trials, the aim of treatment should be to achieve the goals set forth by the American Diabetes Association. Insulin remains an essential therapeutic agent for helping patients achieve glycemic control and preventing long-term comorbidities. However, barriers to insulin therapy exist for both the physician and patient. Strategies to counter this resistance include identifying barriers to treatment, restoring the patient's sense of control, utilizing simple regimens, and reviewing the benefits of insulin and the risk of hypoglycemia. In treating African-American patients with diabetes, providers of various racial and ethnic backgrounds may maximize treatment efficacy by attempting to understand and practice culturally competent care. PMID:17722663

  3. Rural Veteran Access to Healthcare Services: Investigating the Role of Information and Communication Technologies in Overcoming Spatial Barriers

    PubMed Central

    Schooley, Benjamin L; Horan, Thomas A; Lee, Pamela W; West, Priscilla A

    2010-01-01

    This multimethod pilot study examined patient and practitioner perspectives on the influence of spatial barriers to healthcare access and the role of health information technology in overcoming these barriers. The study included a survey administered to patients attending a Department of Veterans Affairs (VA) health visit, and a focus group with VA care providers. Descriptive results and focus group findings are presented. Spatial distance is a significant factor for many rural veterans when seeking healthcare. For this sample of rural veterans, a range of telephone, computer, and Internet technologies may become more important for accessing care as Internet access becomes more ubiquitous and as younger veterans begin using the VA health system. The focus group highlighted the negative impact of distance, economic considerations, geographic barriers, and specific medical conditions on access to care. Lack of adequate technology infrastructure was seen as an obstacle to utilization. This study discusses the need to consider distance, travel modes, age, and information technology infrastructure and adoption when designing health information technology to care for rural patients. PMID:20697468

  4. Enhanced intranasal delivery of mRNA vaccine by overcoming the nasal epithelial barrier via intra- and paracellular pathways.

    PubMed

    Li, Man; Zhao, Mengnan; Fu, Yao; Li, You; Gong, Tao; Zhang, Zhirong; Sun, Xun

    2016-04-28

    Facing the threat of highly variable virus infection, versatile vaccination systems are urgently needed. Intranasal mRNA vaccination provides a flexible and convenient approach. However, the nasal epithelium remains a major biological barrier to deliver antigens to nasal associated lymphoid tissue (NALT). To address this issue, a potent polymer-based intranasal mRNA vaccination system for HIV-1 treatment was synthesized using cationic cyclodextrin-polyethylenimine 2k conjugate (CP 2k) complexed with anionic mRNA encoding HIV gp120. The delivery vehicle containing CP 2k and mRNA overcame the epithelial barrier by reversibly opening the tight junctions, enhanced the paracellular delivery of mRNA and consequently minimized absorption of toxins in the nasal cavity. Together with the excellent intracellular delivery and prolonged nasal residence time, strong system and mucosal anti-HIV immune responses as well as cytokine productions were achieved with a balanced Th1/Th2/Th17 type. Our study provided the first proof of evidence that cationic polymers can be used as safe and potent intranasal mRNA vaccine carriers to overcome the nasal epithelial barrier. The safe and versatile polymeric delivery system represents a promising vaccination platform for infectious diseases.

  5. Rural veteran access to healthcare services: investigating the role of information and communication technologies in overcoming spatial barriers.

    PubMed

    Schooley, Benjamin L; Horan, Thomas A; Lee, Pamela W; West, Priscilla A

    2010-04-01

    This multimethod pilot study examined patient and practitioner perspectives on the influence of spatial barriers to healthcare access and the role of health information technology in overcoming these barriers. The study included a survey administered to patients attending a Department of Veterans Affairs (VA) health visit, and a focus group with VA care providers. Descriptive results and focus group findings are presented. Spatial distance is a significant factor for many rural veterans when seeking healthcare. For this sample of rural veterans, a range of telephone, computer, and Internet technologies may become more important for accessing care as Internet access becomes more ubiquitous and as younger veterans begin using the VA health system. The focus group highlighted the negative impact of distance, economic considerations, geographic barriers, and specific medical conditions on access to care. Lack of adequate technology infrastructure was seen as an obstacle to utilization. This study discusses the need to consider distance, travel modes, age, and information technology infrastructure and adoption when designing health information technology to care for rural patients.

  6. Overcoming restriction as a barrier to DNA transformation in Caldicellulosiruptor species results in efficient marker replacement

    PubMed Central

    2013-01-01

    Background Thermophilic microorganisms have special advantages for the conversion of plant biomass to fuels and chemicals. Members of the genus Caldicellulosiruptor are the most thermophilic cellulolytic bacteria known. They have the ability to grow on a variety of non-pretreated biomass substrates at or near ~80°C and hold promise for converting biomass to bioproducts in a single step. As for all such relatively uncharacterized organisms with desirable traits, the ability to genetically manipulate them is a prerequisite for making them useful. Metabolic engineering of pathways for product synthesis is relatively simple compared to engineering the ability to utilize non-pretreated biomass. Results Here we report the construction of a deletion of cbeI (Cbes2438), which encodes a restriction endonuclease that is as a major barrier to DNA transformation of C. bescii. This is the first example of a targeted chromosomal deletion generated by homologous recombination in this genus and the resulting mutant, JWCB018 (ΔpyrFA ΔcbeI), is readily transformed by DNA isolated from E. coli without in vitro methylation. PCR amplification and sequencing suggested that this deletion left the adjacent methyltransferase (Cbes2437) intact. This was confirmed by the fact that DNA isolated from JWCB018 was protected from digestion by CbeI and HaeIII. Plasmid DNA isolated from C. hydrothermalis transformants were readily transformed into C. bescii. Digestion analysis of chromosomal DNA isolated from seven Caldicellulosiruptor species by using nine different restriction endonucleases was also performed to identify the functional restriction-modification activities in this genus. Conclusion Deletion of the cbeI gene removes a substantial barrier to routine DNA transformation and chromosomal modification of C. bescii. This will facilitate the functional analyses of genes as well as metabolic engineering for the production of biofuels and bioproducts from biomass. An analysis of

  7. Autism and Overcoming Job Barriers: Comparing Job-Related Barriers and Possible Solutions in and outside of Autism-Specific Employment

    PubMed Central

    Lorenz, Timo; Frischling, Cora; Cuadros, Raphael; Heinitz, Kathrin

    2016-01-01

    The aim of this study was to discover how individuals with autism succeed in entering the job market. We therefore sought to identify expected and occurred barriers, keeping them from taking up and staying in employment as well as to identify the solutions used to overcome these barriers. Sixty-six employed individuals with autism–17 of them with autism-specific employment–participated in an online survey. Results showed a variety of possible barriers. Individuals in autism-specific employment named formality problems–problems with organizational and practical process-related aspects of the job entry–most frequently while individuals in non-autism-specific employment mentioned social problems–obstacles concerning communication and human interaction–most. In terms of solutions, both groups used their own resources as much as external help, but differed in their specific strategies. In addition, correlations of an autism-specific employment with general and occupational self-efficacy as well as life and job satisfaction were examined. Possible implications of the results are discussed with regard to problem solving behavior and the use of strengths. PMID:26766183

  8. Sustainable fuel, food, fertilizer and ecosystems through a global artificial photosynthetic system: overcoming anticompetitive barriers

    PubMed Central

    Bruce, Alex; Faunce, Thomas

    2015-01-01

    This article discusses challenges that artificial photosynthetic (AP) systems will face when entering and competing in a global market characterized by established fossil fuel technology. It provides a perspective on the neoliberal principles underpinning much policy entrenching such environmentally destructive technology and outlines how competition law could aid overcoming these hurdles for AP development. In particular, it critiques the potential for competition law to promote a global AP initiative with greater emphasis on atmospheric carbon dioxide and nitrogen fixation (as well as solar-driven water splitting) to produce an equitable, globally distributed source of human food, fertilizer and biosphere sustainability, as well as hydrogen-based fuel. Some relevant strategies of competition law evaluated in this context include greater citizen–consumer involvement in shaping market values, legal requirements to factor services from the natural environment (i.e. provision of clean air, water, soil pollution degradation) into corporate costs, reform of corporate taxation and requirements to balance maximization of shareholder profit with contribution to a nominated public good, a global financial transactions tax, as well as prohibiting horizontal cartels, vertical agreements and unilateral misuse of market power. PMID:26052427

  9. Mucosal Vaccination Overcomes the Barrier to Recombinant Vaccinia Immunization Caused by Preexisting Poxvirus Immunity

    NASA Astrophysics Data System (ADS)

    Belyakov, Igor M.; Moss, Bernard; Strober, Warren; Berzofsky, Jay A.

    1999-04-01

    Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c. immunization with vaccinia induces cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and not in mucosal sites, we hypothesized that the mucosal immune system remains naive to vaccinia and therefore amenable to immunization with recombinant vaccinia vectors despite earlier vaccinia exposure. We show that mucosal immunization of vaccinia-immune BALB/c mice with recombinant vaccinia expressing HIV gp160 induced specific serum antibody and strong HIV-specific cytotoxic T lymphocyte responses. These responses occurred not only in mucosal but also in systemic lymphoid tissue, whereas systemic immunization was ineffective under these circumstances. In this context, intrarectal immunization was more effective than intranasal immunization. Boosting with a second dose of recombinant vaccinia was also more effective via the mucosal route. The systemic HIV-specific cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the mucosal site. These results also demonstrate the independent compartmentalization of the mucosal versus systemic immune systems and the asymmetric trafficking of lymphocytes between them. This approach to circumvent previous vaccinia immunity may be useful for induction of protective immunity against infectious diseases and cancer in the sizable populations with preexisting immunity to vaccinia from smallpox vaccination.

  10. Sustainable fuel, food, fertilizer and ecosystems through a global artificial photosynthetic system: overcoming anticompetitive barriers.

    PubMed

    Bruce, Alex; Faunce, Thomas

    2015-06-06

    This article discusses challenges that artificial photosynthetic (AP) systems will face when entering and competing in a global market characterized by established fossil fuel technology. It provides a perspective on the neoliberal principles underpinning much policy entrenching such environmentally destructive technology and outlines how competition law could aid overcoming these hurdles for AP development. In particular, it critiques the potential for competition law to promote a global AP initiative with greater emphasis on atmospheric carbon dioxide and nitrogen fixation (as well as solar-driven water splitting) to produce an equitable, globally distributed source of human food, fertilizer and biosphere sustainability, as well as hydrogen-based fuel. Some relevant strategies of competition law evaluated in this context include greater citizen-consumer involvement in shaping market values, legal requirements to factor services from the natural environment (i.e. provision of clean air, water, soil pollution degradation) into corporate costs, reform of corporate taxation and requirements to balance maximization of shareholder profit with contribution to a nominated public good, a global financial transactions tax, as well as prohibiting horizontal cartels, vertical agreements and unilateral misuse of market power.

  11. Obtaining family consent for participation in Alzheimer's research in a Cuban-American population: strategies to overcome the barriers.

    PubMed

    Williams, C L; Tappen, R; Buscemi, C; Rivera, R; Lezcano, J

    2001-01-01

    Cultural values and beliefs affect family attitudes toward participation in research. Significant resistance to allowing their elders with dementia to participate in clinical research was encountered in Cuban-American families. These families expressed concern about disturbing the elder's comfort (tranquilidad) and solitude (soledad). Furthermore, most believed that intervention would be futile. Feelings of guilt associated with nursing home placement may have been exacerbated by the suggestion that active intervention could be effective. Strategies to overcome these barriers included reduced emphasis on the potential superiority of the intervention to be tested, reassurance that contact with research staff was usually appreciated by participants, arrangements to talk with the family as a group about the study, and increased use of Spanish-language consent forms.

  12. Pregnancy options counseling for adolescents: overcoming barriers to care and preserving preference.

    PubMed

    Dobkin, Loren M; Perrucci, Alissa C; Dehlendorf, Christine

    2013-04-01

    Current clinical guidelines for counseling adolescent patients about their pregnancy options fail to give concrete suggestions for how to begin and hold conversations that support patient autonomy, provide accurate and unbiased information, and address barriers to care. Recent research suggests that relative to adult women, adolescents are at increased risk of being denied abortion because they present beyond facilities' gestational age limits. Counseling that neglects to address the structural and developmental challenges that adolescents face when seeking care may contribute to the risk of abortion denial as well as subsequent delays in prenatal care. The task of providing non-directive, patient-centered, evidence-based pregnancy options counseling to an adolescent while ensuring that she receives her chosen course of care in a timely manner is challenging. This article presents a shared decision-making framework and specific suggestions for healthcare providers to support adolescent patients in coming to their decision about whether to continue or terminate an unplanned pregnancy and access follow-up care within the current sociopolitical environment.

  13. OVERCOMING BARRIERS To DIVERSITY IN CHIROPRACTIC PATIENT AND PRACTITIONER POPULATIONS: A COMMENTARY.

    PubMed

    Young, Kenneth J

    2015-01-01

    Increasing the diversity of practitioner and patient populations has been identified as a worthy goal in the chiropractic profession, which has predominantly white male practitioners and white female patients in the USA. Toward that end, 'diversity' has been the topic of several papers and was the theme of a 2012 conference of chiropractic educators. However, generally just the microcosm of the interactions of practitioners with patients or teachers with students has been discussed. The macrocosm of larger societal issues and government policies has not been broached. Examples of issues and policies that affect diversity within a profession include portrayals of, and value judgements on diversity by the media and politicians, as well as public funding for healthcare and education. Diversity was defined in this paper to mean differences in race, sex, sexual orientation, economic status, ethnicity, religion and other life circumstances in a population. The purpose of this paper is to raise awareness of evidence that social issues and government policy affect the diversity of practitioners and patients, and to suggest that the barriers to diversity present in these realms be addressed with a cogent, profession-wide effort in order to help increase the diversity of people involved with chiropractic.

  14. Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.

    PubMed

    Saraiva, Cláudia; Praça, Catarina; Ferreira, Raquel; Santos, Tiago; Ferreira, Lino; Bernardino, Liliana

    2016-08-10

    The blood-brain barrier (BBB) is a vital boundary between neural tissue and circulating blood. The BBB's unique and protective features control brain homeostasis as well as ion and molecule movement. Failure in maintaining any of these components results in the breakdown of this specialized multicellular structure and consequently promotes neuroinflammation and neurodegeneration. In several high incidence pathologies such as stroke, Alzheimer's (AD) and Parkinson's disease (PD) the BBB is impaired. However, even a damaged and more permeable BBB can pose serious challenges to drug delivery into the brain. The use of nanoparticle (NP) formulations able to encapsulate molecules with therapeutic value, while targeting specific transport processes in the brain vasculature, may enhance drug transport through the BBB in neurodegenerative/ischemic disorders and target relevant regions in the brain for regenerative processes. In this review, we will discuss BBB composition and characteristics and how these features are altered in pathology, namely in stroke, AD and PD. Additionally, factors influencing an efficient intravenous delivery of polymeric and inorganic NPs into the brain as well as NP-related delivery systems with the most promising functional outcomes will also be discussed.

  15. Overcoming barriers and thresholds – signaling of oligomeric Aβ through the prion protein to Fyn

    PubMed Central

    2013-01-01

    Evidence has been mounting for an involvement of the prion protein (PrP) in a molecular pathway assumed to play a critical role in the etiology of Alzheimer disease. A currently popular model sees oligomeric amyloid β (oAβ) peptides bind directly to PrP to emanate a signal that causes activation of the cytoplasmic tyrosine kinase Fyn, an essential player in a cascade of events that ultimately leads to NMDA receptor-mediated excitotoxicity and hyper-phosphorylation of tau. The model does not reveal, however, how extracellular binding of oAβ to PrP is communicated across the plasma membrane barrier to affect activation of Fyn. A scenario whereby PrP may adapt a transmembrane topology to affect Fyn activation in the absence of additional partners is currently not supported by evidence. A survey of known candidate PrP interactors leads to a small number of molecules that are known to acquire a transmembrane topology and understood to contribute to Fyn activation. Because multiple signaling pathways converge onto Fyn, a realistic model needs to take into account a reality of Fyn acting as a hub that integrates signals from multiple inhibitory and activating effectors. To clarify the role of PrP in oAβ-dependent excitotoxicity, future studies may need to incorporate experimental designs that can probe the contributions of Fyn modulator pathways and rely on analogous readouts, rather than threshold effects, known to underlie excitotoxic signaling. PMID:23856335

  16. [Google translate is not sufficient to overcome language barriers in neonatal medicine].

    PubMed

    Börner, N; Sponholz, S; König, K; Brodkorb, S; Bührer, C; Roehr, C C

    2013-12-01

    Language barriers hinder the interaction with patients and relatives. The use of language services increases knowledge, satisfaction and the use of medical care and thus improves patient's clinical outcome. The recommended use of professional interpreters (PI) is not always feasible. We tested an online translation tool as an alternative for PI for the transla-tion of standardized sentences from a neonatal doctor-/nurse-relative-interview.Translation of 20 sentences from a German neonatal intensive care unit parent information brochure to English, Portuguese and Arabic, using Google Translate (GT). Assessment of accuracy concerning grammar and content, in a second step simplification of all incorrect sentences, translation by GT and critical re-assessment and evaluation.An average of 42% of the sentences was correctly translated concerning grammar and content. The proportion of incorrectly translated sentences varied between 45-70%. By simpli-fication another 23% were translated correctly.Translations by GT were often incorrect in content and grammar. We suppose that the design of GT, which is a statistical translation engine, might be an explanation for this phenomenon. Presently, GT cannot guarantee unambiguous translations and cannot substitute PIs, only in particular circumstances, the use of GT or similar engines may be justified. For future use of electronic translation services, we suggest to compile a catalogue of sentences containing central information, which can be translated into defined foreign languages without misinterpretation or loss of information.

  17. Drug delivery in overcoming the blood–brain barrier: role of nasal mucosal grafting

    PubMed Central

    Marianecci, Carlotta; Rinaldi, Federica; Hanieh, Patrizia Nadia; Di Marzio, Luisa; Paolino, Donatella; Carafa, Maria

    2017-01-01

    The blood–brain barrier (BBB) plays a fundamental role in protecting and maintaining the homeostasis of the brain. For this reason, drug delivery to the brain is much more difficult than that to other compartments of the body. In order to bypass or cross the BBB, many strategies have been developed: invasive techniques, such as temporary disruption of the BBB or direct intraventricular and intracerebral administration of the drug, as well as noninvasive techniques. Preliminary results, reported in the large number of studies on the potential strategies for brain delivery, are encouraging, but it is far too early to draw any conclusion about the actual use of these therapeutic approaches. Among the most recent, but still pioneering, approaches related to the nasal mucosa properties, the permeabilization of the BBB via nasal mucosal engrafting can offer new potential opportunities. It should be emphasized that this surgical procedure is quite invasive, but the implication for patient outcome needs to be compared to the gold standard of direct intracranial injection, and evaluated whilst keeping in mind that central nervous system diseases and lysosomal storage diseases are chronic and severely debilitating and that up to now no therapy seems to be completely successful. PMID:28184152

  18. Identifying and Overcoming Critical Barriers to Widespread Second Use of PEV Batteries

    SciTech Connect

    Neubauer, J.; Smith, K.; Wood, E.; Pesaran, A.

    2015-02-01

    Both the market penetration of plug-in electric vehicles (PEVs) and deployment of grid-connected energy storage systems are presently restricted by the high cost of batteries. Battery second use (B2U) strategies--in which a single battery first serves an automotive application, then is redeployed into a secondary market--could help address both issues by reducing battery costs to the primary (automotive) and secondary (electricity grid) users. This study investigates the feasibility of and major barriers to the second use of lithium-ion PEV batteries by posing and answering the following critical B2U questions: 1. When will used automotive batteries become available, and how healthy will they be? 2. What is required to repurpose used automotive batteries, and how much will it cost? 3. How will repurposed automotive batteries be used, how long will they last, and what is their value? Advanced analysis techniques are employed that consider the electrical, thermal, and degradation response of batteries in both the primary (automotive) and secondary service periods. Second use applications are treated in detail, addressing operational requirements, economic value, and market potential. The study concludes that B2U is viable and could provide considerable societal benefits due to the large possible supply of repurposed automotive batteries and substantial remaining battery life following automotive service. However, the only identified secondary market large enough to consume the supply of these batteries (utility peaker plant replacement) is expected to be a low margin market, and thus B2U is not expected to affect the upfront cost of PEVs.

  19. Bryozoan diversity around the Falkland and South Georgia Islands: Overcoming Antarctic barriers.

    PubMed

    Figuerola, Blanca; Barnes, David K A; Brickle, Paul; Brewin, Paul E

    2017-05-01

    There are a number of remote archipelagos distributed between 45 and 60 °S. The biota of these islands provide useful information to describe and understand patterns in biodiversity and biogeography as well as potential impacts of climate change on marine ecosystems. They are in key locations either side of the Polar Front but also have limited influence from human activities. Here we investigate one taxon, bryozoans, on South Atlantic shelf habitats of the Falkland (FI) and the sub-Antarctic island of South Georgia (SG). We present new data on spatial distribution in these islands, as well as an analysis of the bryozoological similarities between these and neighbouring regions. A total of 85 species of cheilostome bryozoans (351 samples) were found, belonging to 33 genera, including 18 potentially new genera and 23 new species. Remarkably 65% and 41% of species were reported for the first time at FI and SG, respectively. The highest and the lowest value of species richness and species/genus ratio were found at East (EFI) and West Falkland (WFI), respectively, likely showing a tendency for stronger intrageneric competition. New data from this study were jointly analysed with data from the literature and existing databases, revealing new bathymetric ranges in 32 species. The biogeographic affinities of the bryozoans found give further evidence of the hypothesis of sequential separation of Gondwana and support the changing concept that although the Polar Front acts as a circumpolar biogeographic barrier it is not as impermeable as originally thought. Potential dispersal mechanisms are also discussed.

  20. Applying Risk Science and Stakeholder Engagement to Overcome Environmental Barriers to Marine and Hydrokinetic Energy Projects

    SciTech Connect

    Copping, Andrea E.; Anderson, Richard M.; Van Cleve, Frances B.

    2010-09-20

    The production of electricity from the moving waters of the ocean has the potential to be a viable addition to the portfolio of renewable energy sources worldwide. The marine and hydrokinetic (MHK) industry faces many hurdles, including technology development, challenges of offshore deployments, and financing; however, the barrier most commonly identified by industry, regulators, and stakeholders is the uncertainty surrounding potential environmental effects of devices placed in the water and the permitting processes associated with real or potential impacts. Regulatory processes are not well positioned to judge the severity of harm due to turbines or wave generators. Risks from MHK devices to endangered or protected animals in coastal waters and rivers, as well as the habitats that support them, are poorly understood. This uncertainty raises concerns about catastrophic interactions between spinning turbine blades or slack mooring lines and marine mammals, birds and fish. In order to accelerate the deployment of tidal and wave devices, there is a need to sort through the extensive list of potential interactions that may cause harm to marine organisms and ecosystems, to set priorities for regulatory triggers, and to direct future research. Identifying the risk of MHK technology components on specific marine organisms and ecosystem components can separate perceived from real risk-relevant interactions. Scientists from Pacific Northwest National Laboratory (PNNL) are developing an Environmental Risk Evaluation System (ERES) to assess environmental effects associated with MHK technologies and projects through a systematic analytical process, with specific input from key stakeholder groups. The array of stakeholders interested in the development of MHK is broad, segmenting into those whose involvement is essential for the success of the MHK project, those that are influential, and those that are interested. PNNL and their partners have engaged these groups, gaining

  1. Performance of some new Niño3.4 predictors at overcoming the spring predictability barrier.

    NASA Astrophysics Data System (ADS)

    Miguel, Tasambay-Salazar; Jose, Ortizbevia Maria; Francisco Jose, Alvarez-Garcia; Antonio, Ruizdeelvira

    2016-04-01

    The El Niño-Southern Oscillation (ENSO) phenomenon is the main source of predictability skill in many regions of the world, at seasonal and interannual timescales. Improving ENSO understanding and forecast skill is still one of the main goals of the international seasonal forecast programs. A common feature found in ENSO forecast is the skill predictability barrier, that is the skill drop for forecast across the spring season. In this study ENSO variability is represented by the Niño3.4 Index. Here we will use different seasonal linear stochastic models to test the performance of some new ENSO predictors at overcoming the spring predictability barrier. The benchmarkt is the performance scored by the same predictive scheme when the variables are those of a basic equatorial model representing the 'recharge-discharge' oscillator paradigm. Some of the new predictors, like the Tropical South Atlantic Index, the Tropical North Atlantic Index, the Indian Ocean Dipole Mode or the Pacific Meridional Model have been pointed at by recent studies. Additionally, we propose two new predictors, that take into account the zonal sea surface temperature gradients across the tropical Pacific, the North Tropical Pacific Zonal Gradient and the South Tropical Pacific Zonal Gradient Indexes. We intercompare the performance of the new predictors, by introducing them, one at a time, in a simple, three variables, stochastic predictive scheme. For some seasons and lags, the differences between the skill scored by some of the models that include one of these predictors are important. However, these are diminished when a Full Stochastic Mode set-up is adopted. References. Tasambay Salazar, M.; Ortiz Beviá, M. J.; Alvarez García, F. J.; Ruiz de Elvira Serra, A. The Niño3.4 region predictability beyond the persistence barrier. Tellus A. 2015, 67. doi: 10.3402/tellusa.v67.27457,

  2. Let’s Not Contribute to Disparities: The Best Methods for Teaching Clinicians How to Overcome Language Barriers to Health Care

    PubMed Central

    Jacobs, Elizabeth A.

    2010-01-01

    Clinicians should be educated about how language barriers contribute to disparities for patients with limited English proficiency (LEP). However, educators must avoid developing educational interventions that increase health disparities for LEP patients. For example, studies suggest that teaching “Medical Spanish” or related courses may actually contribute to health care disparities if clinicians begin using these non-English language skills inappropriately with patients. We discuss the risks and benefits of teaching specific cultural competence skills and make evidence-based recommendations for the teaching content and methods for educational interventions focused on overcoming language barriers in health care. At minimum, we suggest such interventions include: (1) the role of language barriers in health disparities, (2) means of overcoming language barriers, (3) how to work with interpreters, (4) identifying and fixing problems in interpreted encounters, and (5) appropriate and safe use of one’s own limited non-English language skills. PMID:20352518

  3. The GEOFAR Project - Geothermal Finance and Awareness in Europeans Regions - Development of new schemes to overcome non-technical barriers, focusing particularly on financial barriers

    NASA Astrophysics Data System (ADS)

    Poux, Adeline; Wendel, Marco; Jaudin, Florence; Hiegl, Mathias

    2010-05-01

    Numerous advantages of geothermal energy like its widespread distribution, a base-load power and availability higher than 90%, a small footprint and low carbon emissions, and the growing concerns about climate changes strongly promote the development of geothermal projects. Geothermal energy as a local energy source implies needs on surface to be located close to the geothermal resource. Many European regions dispose of a good geothermal potential but it is mostly not sufficiently developed due to non-technical barriers occurring at the very early stages of the project. The GEOFAR Project carried out within the framework of EU's "Intelligent Energy Europe" (IEE) program, gathers a consortium of European partners from Germany, France, Greece, Spain and Portugal. Launched in September 2008, the aim of this research project is to analyze the mentioned non-technical barriers, focusing most particularly on economic and financial aspects. Based on this analysis GEOFAR aims at developing new financial and administrative schemes to overcome the main financial barriers for deep geothermal projects (for electricity and direct use, without heat pumps). The analysis of the current situation and the future development of geothermal energy in GEOFAR target countries (Germany, France, Greece, Spain, Portugal, Slovakia, Bulgaria and Hungary) was necessary to understand and expose the diverging status of the geothermal sector and the more and less complicated situation for geothermal projects in different Europeans Regions. A deeper analysis of 40 cases studies (operating, planned and failed projects) of deep geothermal projects also contributed to this detailed view. An exhaustive analysis and description of financial mechanisms already existing in different European countries and at European level to support investors completed the research on non-technical barriers. Based on this profound analysis, the GEOFAR project has made an overview of the difficulties met by project

  4. miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers to Spinal Cord Repair

    PubMed Central

    Mandrekar-Colucci, Shweta; Hall, Jodie C.E.; Sweet, David R.; Schmitt, Philipp J.; Xu, Xinyang; Guan, Zhen; Mo, Xiaokui; Guerau-de-Arellano, Mireia

    2016-01-01

    Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers including inflammation. microRNA (miR)-155–5p is a small, noncoding RNA that negatively regulates mRNA translation. In macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response that could be toxic after SCI. miR-155 may also independently alter expression of genes that regulate axon growth in neurons. Here, we hypothesized that miR-155 deletion would simultaneously improve axon growth and reduce neuroinflammation after SCI by acting on both neurons and macrophages. New data show that miR-155 deletion attenuates inflammatory signaling in macrophages, reduces macrophage-mediated neuron toxicity, and increases macrophage-elicited axon growth by ∼40% relative to control conditions. In addition, miR-155 deletion increases spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG) neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion augments conditioning lesion-induced intraneuronal expression of SPRR1A, a regeneration-associated gene; ∼50% more injured KO DRG neurons expressed SPRR1A versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced axon regeneration beyond the epicenter. Finally, in a model of spinal contusion injury, miR-155 deletion improves locomotor function at postinjury times corresponding with the arrival and maximal appearance of activated intraspinal macrophages. In miR-155 KO mice, improved locomotor function is associated with smaller contusion lesions and decreased accumulation of inflammatory macrophages. Collectively, these data indicate that miR-155 is a novel therapeutic target capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic barriers to repair after SCI. SIGNIFICANCE STATEMENT Axon regeneration after spinal cord injury (SCI) fails

  5. Overcoming access barriers to health services through membership-based microfinance organizations: a review of evidence from South Asia.

    PubMed

    Saha, Somen; Annear, Peter Leslie

    2014-06-30

    It is a challenge for the poor to overcome the barriers to accessing health services. Membership-based microfinance with associated health programmes can improve health outcomes for the poor. This study reviewed the evidence published between 1993 and 2013 on the role of membership-based microfinance with associated health programmes in improving health outcomes for the poor in South Asia. A total of 661 papers were identified and 26 selected for inclusion, based on the relevance and rigour of the research methods. Of these 26, five were evidence reviews. Of the remaining 21 papers, 12 were from India, seven from Bangladesh, and one each from Sri Lanka and Indonesia. Three papers addressed more than one theme. Five key themes emerged from the review: (i) the impact of microfinance programmes on the social and economic situation of the poor; (ii) the impact of microfinance programmes on community health; (iii) the impact of integrated microfinance health programmes on raising client awareness; (iv) the impact of integrated microfinance health programmes on financing health care; and (v) the impact of integrated microfinance health programmes on affordable health-care products and services. The review provides new evidence on the pathways through which microfinance helps to improve population health and value for money for such programmes. Among countries with large populations in the informal sector, there is a strong case for policy-makers to support these groups in providing access to life-saving health care among the poor.

  6. Overcoming access barriers to health services through membership-based microfinance organizations: a review of evidence from South Asia

    PubMed Central

    Saha, Somen; Annear, Peter Leslie

    2015-01-01

    It is a challenge for the poor to overcome the barriers to accessing health services. Membership-based microfinance with associated health programmes can improve health outcomes for the poor. This study reviewed the evidence published between 1993 and 2013 on the role of membership-based microfinance with associated health programmes in improving health outcomes for the poor in South Asia. A total of 661 papers were identified and 26 selected for inclusion, based on the relevance and rigour of the research methods. Of these 26, five were evidence reviews. Of the remaining 21 papers, 12 were from India, seven from Bangladesh, and one each from Sri Lanka and Indonesia. Three papers addressed more than one theme. Five key themes emerged from the review: (i) the impact of microfinance programmes on the social and economic situation of the poor; (ii) the impact of microfinance programmes on community health; (iii) the impact of integrated microfinance health programmes on raising client awareness; (iv) the impact of integrated microfinance health programmes on financing health care; and (v) the impact of integrated microfinance health programmes on affordable health-care products and services. The review provides new evidence on the pathways through which microfinance helps to improve population health and value for money for such programmes. Among countries with large populations in the informal sector, there is a strong case for policy-makers to support these groups in providing access to life-saving health care among the poor. PMID:25685728

  7. The role of "blebbing" in overcoming the hydrophobic barrier during biooxidation of elemental sulfur by Thiobacillus thiooxidans

    USGS Publications Warehouse

    Knickerbocker, C.; Nordstrom, D.K.; Southam, G.

    2000-01-01

    Brimstone Basin, in southeastern Yellowstone National Park, Wyoming is an ancient hydrothermal area containing solfataric alteration. Drainage waters flowing from Brimstone Basin had pH values as low as 1.23 and contained up to 1.7×106 MPN/ml acidophilic sulfur-oxidizing bacteria. Thiobacillus thiooxidans was the dominant sulfur-oxidizing bacterium recovered from an enrichment culture and was used in a structural examination of bacterial sulfur oxidation. Growth in these sulfur cultures occurred in two phases with cells in association with the macroscopic sulfur grains and in suspension above these grains. Colonization of sulfur grains by individual cells and microcolonies was facilitated by organic material that appeared to be responsible for bacterial adhesion. Transmission electron microscopy of negatively stained (2% [wt./vol.] uranyl acetate), sulfur-grown T. thiooxidans revealed extensive membrane blebbing (sloughing of outer membrane vesicles) and the presence of approximately 100 nm sized sulfur particles adsorbed to membrane material surrounding individual bacteria. Sulfite-grown bacteria did not possess membrane blebs. The amphipathic nature of these outer membrane vesicles appear to be responsible for overcoming the hydrophobic barrier necessary for the growth of T. thiooxidans on elemental sulfur.

  8. "My hair or my health:" Overcoming barriers to physical activity in African American women with a focus on hairstyle-related factors.

    PubMed

    Huebschmann, Amy G; Campbell, Lucille Johnson; Brown, Candace S; Dunn, Andrea L

    2016-01-01

    Physical activity disparities among African American (AA) women may be related to sociocultural barriers, including difficulties with restyling hair after exercise. We sought to identify physical activity barriers and facilitators in AA women with a focus on sociocultural factors related to hairstyle maintenance. Participants (n = 51) were AA women aged 19-73 years who completed valid surveys and participated in structured focus groups, stratified by age and physical activity levels, from November 2012 to February 2013. The Constant Comparison method was used to develop qualitative themes for barriers and facilitators. The most frequently reported general physical activity barrier among exercisers was "lack of money" (27%) and among non-exercisers was "lack of self-discipline" (57%). A hairstyle-related barrier of "sweating out my hairstyle" was reported by 7% of exercisers and 29% of non-exercisers. This hairstyle-related barrier included the need for extra time and money to restyle hair due to perspiration. Hairstyle-related facilitators included: prioritizing health over hairstyle and high self-efficacy to restyle hair after perspiration. Participants were interested in resources to simplify hairstyle maintenance. AA women whose hairstyle is affected by perspiration may avoid physical activity due to time and financial burdens. Increasing self-efficacy to restyle hair after perspiration may help to overcome this barrier.

  9. Sterically hindered complexes of platinum(II) with planar heterocyclic nitrogen donors. A novel complex with 1-methyl-cytosine has a spectrum of activity different from cisplatin and is able of overcoming acquired cisplatin resistance.

    PubMed

    Margiotta, Nicola; Natile, Giovanni; Capitelli, Francesco; Fanizzi, Francesco P; Boccarelli, Angelina; De Rinaldis, Pietro; Giordano, Domenico; Coluccia, Mauro

    2006-11-01

    A very interesting series of water soluble platinum compounds violating some of the classical structure-activity relationships, but still showing antitumor activity, was reported by Hollis and collaborators some 25 years ago [L.S. Hollis, A.R. Amundsenm, E.W. Stern. J. Med. Chem. 32 (1989) 128-136]. The compounds, having formula [PtClA(2)L](+) (A(2)=two monodentate or a bidentate amine, L=a secondary or tertiary amine or a N-donor heterocycle), were characterized by a positive charge and three non-labile N-donor ligands. We have extended the investigation to analogous compounds in which 2,9-dimethyl-1,10-phenanthroline has taken the place of the A(2) ligand(s) and L is 2-picoline (1), 6-amino-2-picoline (2), or 1-methyl-cytosine (3). The X-ray analysis of 2 has revealed a bow-like distortion of the phenanthroline plane, a sloping of the phenanthroline plane with respect to the coordination plane, and an overall shielding of the metallic core by the ortho substituents of the phenanthroline and pyridine ligands. In vitro grow inhibition assays have been performed on the most water soluble complex 3. The results indicate that this complex is characterized by a potent growth inhibitory activity with mean IC(50) value (in a panel of 11 human tumor cell lines) of 1.1 microM to be compared with a mean value of 3.8 microM for cisplatin. The same compound also appears to completely overcome the acquired cisplatin resistance stemming from reduced uptake or a multifocal mechanism, thus pointing to a mechanism of action distinctly different from that of cisplatin.

  10. What Are the Barriers Which Discourage 15-16 Year-Old Girls from Participating in Team Sports and How Can We Overcome Them?

    PubMed Central

    Wetton, Abigail R.; Jones, Angela R.; Pearce, Mark S.

    2013-01-01

    Given the clear benefits of regular physical activity (such as reduced risks of cardiovascular disease and obesity, as well as other benefits including those related to mental health), exploration of the reasons that adolescent girls give for not taking part in team sports may be particularly valuable for enhancing later rates of participation. We combined questionnaires (n = 60) and semistructured interviews (n = 6) to assess the barriers that prevent 15-16-year-old girls from participating in extracurricular team games and what can be done to overcome these barriers and improve physical activity levels. Four barriers became prominent as to why girls in this sample do not participate: Internal Factors, Existing Stereotypes, Other Hobbies and Teachers. Methods to overcome these barriers were identified; changing teachers' attitudes and shifting the media's focus away from male sport. Following the successful summer Olympics and Paralympics in the UK, and the resulting positive focus on some of the nation's female athletes, a shift in focus may be possible. However, this needs to be maintained to allow girls more opportunities, role models and motivation to participate in sport. PMID:24073416

  11. What are the barriers which discourage 15-16 year-old girls from participating in team sports and how can we overcome them?

    PubMed

    Wetton, Abigail R; Radley, Rebecca; Jones, Angela R; Pearce, Mark S

    2013-01-01

    Given the clear benefits of regular physical activity (such as reduced risks of cardiovascular disease and obesity, as well as other benefits including those related to mental health), exploration of the reasons that adolescent girls give for not taking part in team sports may be particularly valuable for enhancing later rates of participation. We combined questionnaires (n = 60) and semistructured interviews (n = 6) to assess the barriers that prevent 15-16-year-old girls from participating in extracurricular team games and what can be done to overcome these barriers and improve physical activity levels. Four barriers became prominent as to why girls in this sample do not participate: Internal Factors, Existing Stereotypes, Other Hobbies and Teachers. Methods to overcome these barriers were identified; changing teachers' attitudes and shifting the media's focus away from male sport. Following the successful summer Olympics and Paralympics in the UK, and the resulting positive focus on some of the nation's female athletes, a shift in focus may be possible. However, this needs to be maintained to allow girls more opportunities, role models and motivation to participate in sport.

  12. Advocating for responsible oil and natural gas extraction policies; FracTracker as a mechanism for overcoming the barriers to scientific advocacy for academics and communities

    NASA Astrophysics Data System (ADS)

    Ferrar, K. J.; Malone, S.; Kelso, M.; Lenker, B.

    2013-12-01

    The inability to translate data to scientific information that can readily be incorporated by citizens into the public arena is an obstacle for science-based advocacy. This issue is particularly poignant for shale oil and natural gas development via hydraulic fracturing, as the issue has become highly politicized. Barriers to engaging in policy debate are different but highly related for community members and scientists. For citizens and interest groups, barriers including accessibility, public awareness and data presentation limit the motivation for community involvement in political interactions. To overcome such barriers, social researchers call for public engagement to move upstream and many call for a broad engagement of scientists in science-based advocacy. Furthermore surveys have shown that citizens, interest groups, and decision-makers share a broad desire for scientists to engage in environmental policy development. Regardless, scientists face a number of perceived barriers, with academics expressing the most resistance to overcoming the tension created by adherence to the scientific method and the need to engage with the broader society, described by Schneider (1990) as the 'double ethical bind'. For the scientific community the appeal of public dissemination of information beyond the scope of academic journals is limited for a number of reasons. Barriers include preservation of credibility, peer attitudes, training, and career trajectory. The result is a lack of translated information available to the public. This systematic analysis of the FracTracker platform provides an evaluation of where the features of the public engagement, GIS platform has been successful at overcoming these barriers to public dissemination, where the platform needs further development or is ill-suited to address these issues, and the development of FracTracker as an outlet for scientific researchers to engage with citizens. The analysis will also provide insight into what

  13. [How are Pediatric Hospitals in North-Rhine Westfalia Prepared to Overcome Language Barriers? A Pilot Study Exploring The Structural Quality of Inpatient Care].

    PubMed

    Langer, T; Zapf, T; Wirth, S; Meyer, B; Wiegand, A; Timmen, H; Gupta, S J; Schuster, S; Geraedts, M

    2016-05-04

    Background: In Germany, 35% of all children are considered to have a "migration background", and in the state of North-Rhine-Westfalia 43%. Frequently, one or both parents of a patient with a migration background have limited German language proficiency. Communication barriers due to a language difference can have a negative impact on quality of care, patient safety and costs of care. In this study, we investigate how children's hospitals are prepared to meet the challenges associated with language barriers. Methods: We surveyed all children's hospitals in the state of North-Rhine-Westfalia, Germany. The questionnaire was based on the "Standards for Culturally and Linguistically Appropriate Services in Health and Health Care (CLAS)" and was adapted to circumstances in Germany. Results: Thirty-eight hospitals participated (51%) in this survey. Language barriers occurred frequently (75% of respondents mentioned language difficulties in more than 10% of the patient population). 82% of respondents rated their hospital to be "less than well prepared" to overcome language barriers. In the majority of hospitals (62%), the need for an interpreter was determined on a case-to-case basis and not according to any set protocol. In most cases bilingual staff was used for interpreting. However, only 38% of respondents found a list of available bilingual staff to be a sufficient resource. 42% of respondents did not know the monthly costs for professional interpreting services. In the remaining cases, costs were less than € 500/month. Conclusion: To overcome language barriers, hospitals rely on local resources. The majority of respondents did not find them to be appropriate and sufficient. The development of quality standards and the provision of financial resources are necessary to mobilize this potential for improvement. Therefore, other disciplines and sectors of healthcare need to be analyzed in order to provide the evidence for a constructive discussion with decision

  14. Strategies to Overcome Barriers to Implementation of Alcohol Screening and Brief Intervention in General Practice: a Delphi Study Among Healthcare Professionals and Addiction Prevention Experts.

    PubMed

    Abidi, L; Oenema, A; Nilsen, P; Anderson, P; van de Mheen, D

    2016-08-01

    Despite the evidence base, alcohol screening and brief intervention (ASBI) have rarely been integrated into routine clinical practice. The aim of this study is to identify strategies that could tackle barriers to ASBI implementation in general practice by involving primary healthcare professionals and addiction prevention experts. A three-round online Delphi study was carried out in the Netherlands. The first-round questionnaire consisted of open-ended questions to generate ideas about strategies to overcome barriers. In the second round, participants were asked to indicate how applicable they found each strategy. Items without consensus were systematically fed back with group median ratings and interquartile range (IQR) scores in the third-round questionnaire. In total, 39 out of 69 (57 %) invited participants enrolled in the first round, 214 participants completed the second round, and 144 of these (67 %) completed the third-round questionnaire. Results show that participants reached consensus on 59 of 81 strategies, such as the following: (1) use of E-learning technology, (2) symptom-specific screening by general practitioners (GPs) and/or universal screening by practice nurses, (3) reimbursement incentives, (4) supportive materials, (5) clear guidelines, (6) service provision of addiction care centers, and (7) more publicity in the media. This exploratory study identified a broad set of strategies that could potentially be used for overcoming barriers to ASBI implementation in general practice and paves the way for future research to experimentally test the identified implementation strategies using multifaceted approaches.

  15. Overcoming language barriers in the informed consent process: regulatory and compliance issues with the use of the "short form".

    PubMed

    Lad, Pramod M; Dahl, Rebecca

    2014-01-01

    Language barriers in the informed consent process can be a significant impediment when recruiting non-English speaking subjects into clinical research studies. Regulatory guidelines indicate that the short form procedure be utilized in such circumstances. In this paper, we examine some of the ambiguities in the regulatory framework, the resulting need for institutional policy guidelines, and compliance issues with the short form process.

  16. "We Don't Want to Talk about That": Overcoming Barriers to Rural Aging Research and Interventions on Sensitive Topics

    ERIC Educational Resources Information Center

    Zanjani, Faika; Rowles, Graham D.

    2012-01-01

    Geographical, economic, social and cultural barriers to accessing services in rural areas are widely reported. Less widely discussed are dilemmas posed by individual and community reluctance to address sensitive health issues. This article, focusing on the highly sensitive area of mental health, and employing a participatory action approach,…

  17. Overcoming barriers to effectiveness in a health care operational environment: building on the lessons of American industry.

    PubMed

    Zimmerer, L W; Zimmerer, T W; Yasin, M M

    1999-01-01

    Several of the manufacturing-based philosophies, techniques and tools, such as Total Quality Management (TQM), Continuous Improvement (CI), Business Process Reengineering (BPR) and Time-based Competition (TBC) have been successfully adapted for use within the service sector. Diverse service industries including airlines, insurance, food services and hospitality have increased customer satisfaction and performance through the use of the quality driven, manufacturing-based philosophies. This article explores the reasons for the limited success of TQM/CI, BPR, TBC and benchmarking within the health care industry. Sixteen barriers to change are identified, possible counter-measures to these barriers are outlined and two conceptual frameworks are offered as possible facilitators of change for the health care industry.

  18. Being "chill" with teachers and "frozen" by peers in science: overcoming social and educational barriers in a learning community

    NASA Astrophysics Data System (ADS)

    Kim, Hannah; Scantlebury, Kathryn

    2013-09-01

    This forum discusses the issue of `othering' and how intersectionality is a useful analytical framework for understanding the students' immigrant experiences in, and out of, the science classroom. We use a feminist perspective to discuss Minjung's study because gender is a key aspect of one's identity other aspects such as race, religion, socio-economic status, and age have assumed a significant status in gender studies. Lastly we examine the supports and barriers that cliques can produce and propose the importance of building a learning community in the science classroom to engage all students.

  19. Using community-based participatory research to identify potential interventions to overcome barriers to adolescents’ healthy eating and physical activity

    PubMed Central

    Goh, Ying-Ying; Sipple-Asher, Bessie Ko; Uyeda, Kimberly; Hawes-Dawson, Jennifer; Olarita-Dhungana, Josephina; Ryan, Gery W.; Schuster, Mark A.

    2010-01-01

    Using a community-based participatory research approach, we explored adolescent, parent, and community stakeholder perspectives on barriers to healthy eating and physical activity, and intervention ideas to address adolescent obesity. We conducted 14 adolescent focus groups (n = 119), 8 parent focus groups (n = 63), and 28 interviews with community members (i.e., local experts knowledgeable about youth nutrition and physical activity). Participants described ecological and psychosocial barriers in neighborhoods (e.g., lack of accessible nutritious food), in schools (e.g., poor quality of physical education), at home (e.g., sedentary lifestyle), and at the individual level (e.g., lack of nutrition knowledge). Participants proposed interventions such as nutrition classes for families, addition of healthy school food options that appeal to students, and non-competitive physical education activities. Participants supported health education delivered by students. Findings demonstrate that community-based participatory research is useful for revealing potentially feasible interventions that are acceptable to community members. PMID:19544091

  20. Do we need to overcome barriers to learning in the workplace for foundation trainees rotating in neurosurgery in order to improve training satisfaction?

    PubMed

    Phan, Pho Nh; Patel, Keyur; Bhavsar, Amar; Acharya, Vikas

    2016-01-01

    Junior doctors go through a challenging transition upon qualification; this repeats every time they start a rotation in a new department. Foundation level doctors (first 2 years postqualification) in neurosurgery are often new to the specialty and face various challenges that may result in significant workplace dissatisfaction. The neurosurgical environment is a clinically demanding area with a high volume of unwell patients and frequent emergencies - this poses various barriers to learning in the workplace for junior doctors. We identify a number of key barriers and review ideas that can be trialed in the department to overcome them. Through an evaluation of current suggestions in the literature, we propose that learning opportunities need to be made explicit to junior doctors in order to encourage them to participate as a member of the team. We consider ideas for adjustments to the induction program and the postgraduate medical curriculum to shift the focus from medical knowledge to improving confidence and clinical skills in newly qualified doctors. Despite being a powerful window for opportunistic learning, the daily ward round is unfortunately not maximized and needs to be more learner focused while maintaining efficiency and time consumption. Finally, we put forward the idea of an open forum where trainees can talk about their learning experiences, identify subjective barriers, and suggest solutions to senior doctors. This would be achieved through departmental faculty development. These interventions are presented within the context of the neurosurgical ward; however, they are transferable and can be adapted in other specialties and departments.

  1. The Value of Companion Diagnostics: Overcoming Access Barriers to Transform Personalised Health Care into an Affordable Reality in Europe.

    PubMed

    Wurcel, Victoria; Perche, Olivier; Lesteven, Daniel; Williams, Doris-Ann; Schäfer, Birgit; Hopley, Colin; Jungwirth, Rebecca; Postulka, Anne; Pasmans, Raf; Hermansson, Lisse-Lotte; Ott, Markus; Glorioso, Valeria

    2016-01-01

    Personalised health care is an evolution, moving away from a disease-focused model of care, translating scientific and technological advances into benefits for patients, and placing them at the centre of the patients' health and care. Companion diagnostics emerge as a very specific and special group of in vitro diagnostics among the different technologies shaping the personalised health care spectrum. Companion diagnostics provide highly valuable information, allowing patients, health practitioners and payers to decide with a higher level of certainty on the potential benefits of a treatment or care pathway. Decreasing uncertainty may result in a more efficient selection of treatments and care, targeted at subpopulations that are most likely to benefit. Companion diagnostics account for a minimal portion of the already small expenditure on in vitro diagnostics (far less than 1% of total health care expenditure), and yet they provide the means to limit inefficient use of health care resources while optimising patient outcomes. It is clear that equal access to personalised health care is still an issue across the EU. One of the most common perceived barriers is affordability. The investment in companion diagnostics can provide long-term value for patients and health care systems, shifting resources to areas of need. Health systems do not fully recognise yet the value that companion diagnostics bring to make personalised health care more affordable across the EU. This inhibits patient access to personalised treatments and care, preventing improved outcomes. In many countries, market access frameworks for diagnostic tests are fragmented and not aligned with specific funding and reimbursement mechanisms, discouraging the use of these tests. Emerging evidence shows that patients are missing out on the appropriate tests and treatments while a reduction in the inefficient use of health care resources is not realised. This article outlines some of these market access

  2. Overcoming language and cultural barriers: a graphical communication tool to perform a parasitological screening in two vulnerable populations from Argentina.

    PubMed

    Buyayisqui, María Pía; Bordoni, Noemí; Garbossa, Graciela

    2013-01-01

    This is an exploratory study of the application of a support tool for the detection of asymptomatic subjects carrying enteric parasites in two vulnerable populations in Argentina: a shantytown in the city of Buenos Aires and a rural Wichí indigenous community in the province of Chaco. The ethnic and cultural diversity, high illiteracy rate, and language barriers called for the development of an auxiliary resource to explain stool sample collection procedures. In individual interviews with each family, the authors used two instructional guidance leaflets in comic strip format depicting the procedures. They evaluated the acceptance of the graphical communication tool on the basis of the number of retrieved samples. Percentages of respondent families were 72.2% and 66.7%, respectively. Definitive validation of these instruments would allow their use in community studies, community service learning experiences, and research on aboriginal communities that would otherwise be excluded from studies on health status.

  3. A collaborative care telemedicine intervention to overcome treatment barriers for Latina women with depression during the perinatal period.

    PubMed

    Baker-Ericzén, Mary J; Connelly, Cynthia D; Hazen, Andrea L; Dueñas, Cecilia; Landsverk, John A; Horwitz, Sarah McCue

    2012-09-01

    Maternal depression is highly prevalent (10-20%) during the perinatal period, with rates as high as 35% to 40% for Latinas. However, few Latinas are either identified or treated during the perinatal period. The Perinatal Mental Health (PMH) model was designed to ameliorate the barriers that prevent adequate diagnoses and intervention. The PMH is a culturally sensitive, short-term telemedicine, collaborative care intervention for addressing depression among Mexican American mothers. It attends to sociocultural and socioeconomic dimensions and is delivered by trained mental health advisors in obstetric care settings. This article describes the feasibility and acceptability of using the PMH. Participants (N = 79) were selected from a 1st-year ongoing randomized trial in community obstetric clinics. The intervention seems feasible and acceptable; low-income Latinas, identified as depressed during the perinatal period, reported having access to a range of appropriate community services and high satisfaction.

  4. A Collaborative Care Telemedicine Intervention to Overcome Treatment Barriers for Latina Women with Depression during the Perinatal Period

    PubMed Central

    Baker-Ericzén, Mary J.; Connelly, Cynthia D.; Hazen, Andrea L.; Dueñas, Cecilia; Landsverk, John A.; Horwitz, Sarah McCue

    2013-01-01

    Maternal depression is highly prevalent (10 to 20%) during the perinatal period with rates as high as 35 to 40% for Latinas. However, few Latinas are either identified or treated during the perinatal period. To address these disparities, the Perinatal Mental Health Model (PMH) was designed to ameliorate the barriers that prevent adequate diagnoses and intervention. The PMH is a culturally sensitive, short-term telemedicine, and collaborative care intervention for addressing depression among Mexican American mothers. It attends to sociocultural and socioeconomic dimensions and is delivered by trained mental health advisors within obstetric care settings. This article describes the feasibility and acceptability of utilizing the PMH. Participants (n=79) were selected from a first year ongoing randomized trial in community obstetric clinics. The intervention seems feasible and acceptable; low-income Latinas, identified as depressed during the perinatal period, reported having access to a range of appropriate community services and high satisfaction. PMID:22709321

  5. PLANET FORMATION IN STELLAR BINARIES. II. OVERCOMING THE FRAGMENTATION BARRIER IN α CENTAURI AND γ CEPHEI-LIKE SYSTEMS

    SciTech Connect

    Rafikov, Roman R.; Silsbee, Kedron

    2015-01-10

    Planet formation in small-separation (∼20 AU) eccentric binaries such as γ Cephei or α Centauri is believed to be adversely affected by the presence of the stellar companion. Strong dynamical excitation of planetesimals by the eccentric companion can result in collisional destruction (rather than growth) of 1-100 km objects, giving rise to the ''fragmentation barrier'' for planet formation. We revise this issue using a novel description of secular dynamics of planetesimals in binaries, which accounts for the gravity of the eccentric, coplanar protoplanetary disk, as well as gas drag. By studying planetesimal collision outcomes, we show, in contrast to many previous studies, that planetesimal growth and subsequent formation of planets (including gas giants) in AU-scale orbits within ∼20 AU separation binaries may be possible, provided that the protoplanetary disks are massive (≳ 10{sup –2} M {sub ☉}) and only weakly eccentric (disk eccentricity ≲ 0.01). These requirements are compatible with both the existence of massive (several M{sub J} ) planets in γ Cep-like systems and the results of recent simulations of gaseous disks in eccentric binaries. Terrestrial and Neptune-like planets can also form in lower-mass disks at small (sub-AU) radii. We find that the fragmentation barrier is less of a problem in eccentric disks that are apsidally aligned with the binary orbit. Alignment gives rise to special locations, where (1) relative planetesimal velocities are low and (2) the timescale of their drag-induced radial drift is long. This causes planetesimal pileup at such locations in the disk and promotes their growth locally, helping to alleviate the timescale problem for core formation.

  6. Overcoming barriers to seedling regeneration during forest restoration on tropical pasture land and the potential value of woody weeds

    PubMed Central

    Elgar, Amelia T.; Freebody, Kylie; Pohlman, Catherine L.; Shoo, Luke P.; Catterall, Carla P.

    2014-01-01

    Combating the legacy of deforestation on tropical biodiversity requires the conversion to forest of large areas of established pasture, where barriers to native plant regeneration include competition with pasture grasses and poor propagule supply (seed availability). In addition, initial woody plants that colonise pasture are often invasive, non-native species whose ecological roles and management in the context of forest regeneration are contested. In a restoration experiment at two 0.64 ha sites we quantified the response of native woody vegetation recruitment to (1) release from competition with introduced pasture grasses, and (2) local facilitation of frugivore-assisted seed dispersal provided by scattered woody plants and artificial bird perches. Herbicide pasture grass suppression during 20 months caused a significant but modest increase in density of native woody seedlings, together with abundant co-recruitment of the prominent non-native pioneer wild tobacco (Solanum mauritianum). Recruitment of native species was further enhanced by local structure in herbicide-treated areas, being consistently greater under live trees and dead non-native shrubs (herbicide-treated) than in open areas, and intermediate under bird perches. Native seedling recruitment comprised 28 species across 0.25 ha sampled but was dominated by two rainforest pioneers (Homalanthus novoguineensis, Polyscias murrayi). These early results are consistent with the expected increase in woody vegetation recruitment in response to release from competitive and dispersive barriers to rainforest regeneration. The findings highlight the need for a pragmatic consideration of the ecological roles of woody weeds and the potential roles of “new forests” more broadly in accelerating succession of humid tropical forest across large areas of retired agricultural land. PMID:24904602

  7. Obtaining family consent for participation in Alzheimer’s research in a Cuban-American population: Strategies to overcome the barriers

    PubMed Central

    Williams, Christine L.; Tappen, Ruth; Buscemi, Charles; Rivera, Richard; Lezcano, Jennifer

    2007-01-01

    Cultural values and beliefs affect family attitudes toward participation in research. Significant resistance to allowing their elders with dementia to participate in clinical research was encountered in Cuban-American families. These families expressed concern about disturbing the elder’s comfort (tranquilidad) and solitude (soledad) Furthermore, most believed that intervention would be futile. Feelings of guilt associated with nursing home placement may have been exacerbated by the suggestion that active intervention could be effective. Strategies to overcome these barriers included reduced emphasis on the potential superiority of the intervention to be tested, reassurance that contact with research staff was usually appreciated by participants, arrangements to talk with the family as a group about the study, and increased use of Spanish-language consent forms. PMID:11398568

  8. The Long Way From Government Open Data to Mobile Health Apps: Overcoming Institutional Barriers in the US Federal Government

    PubMed Central

    2014-01-01

    Background Government agencies in the United States are creating mobile health (mHealth) apps as part of recent policy changes initiated by the White House’s Digital Government Strategy. Objective The objective of the study was to understand the institutional and managerial barriers for the implementation of mHealth, as well as the resulting adoption pathways of mHealth. Methods This article is based on insights derived from qualitative interview data with 35 public managers in charge of promoting the reuse of open data through Challenge.gov, the platform created to run prizes, challenges, and the vetting and implementation of the winning and vendor-created apps. Results The process of designing apps follows three different pathways: (1) entrepreneurs start to see opportunities for mobile apps, and develop either in-house or contract out to already vetted Web design vendors; (2) a top-down policy mandates agencies to adopt at least two customer-facing mobile apps; and (3) the federal government uses a policy instrument called “Prizes and Challenges”, encouraging civic hackers to design health-related mobile apps using open government data from HealthData.gov, in combination with citizen needs. All pathways of the development process incur a set of major obstacles that have to be actively managed before agencies can promote mobile apps on their websites and app stores. Conclusions Beyond the cultural paradigm shift to design interactive apps and to open health-related data to the public, the managerial challenges include accessibility, interoperability, security, privacy, and legal concerns using interactive apps tracking citizen. PMID:25537314

  9. Socio-ecological Model as a Framework for Overcoming Barriers and Challenges in Randomized Control Trials in Minority and Underserved Communities

    PubMed Central

    Salihu, Hamisu M.; Wilson, Ronee E.; King, Lindsey M.; Marty, Phillip J.; Whiteman, Valerie E.

    2015-01-01

    Background: Numerous barriers and challenges can hinder the successful enrollment and retention of study participants in clinical trials targeting minority populations. To conduct quality research, it is important to investigate these challenges, determine appropriate strategies that are evidence-based and continue seeking methods of improvement. Methods: In this paper, we report such experiences in a registered clinical trial in an underserved minority population in the Southern part of United States. This research study is a randomized double-blind controlled clinical trial that tests the efficacy of higher-strength as compared to low-strength/standard of care folic acid to prevent fetal body and brain size reduction in pregnant women who smoke. A unique approach in this socio-behavioral, genetic-epigenetic clinical trial is that we have adopted the socio-ecological model as a functional platform to effectively achieve and maintain high participant recruitment and retention rates. Results: We highlight the barriers we have encountered in our trial and describe how we have successfully applied the socio-ecological model to overcome these obstacles. Conclusions and Global Health Implications: Our positive experience will be of utility to other researchers globally. Our fi ndings have far-reaching implications as the socio-ecological model approach is adaptable to developed and developing regions and has the potential to increase recruitment and retention of hard-to-reach populations who are typically under-represented in clinical trials. PMID:27621990

  10. Collective epithelial cell invasion overcomes mechanical barriers of collagenous extracellular matrix by a narrow tube-like geometry and MMP14-dependent local softening†

    PubMed Central

    Alcaraz, Jordi; Mori, Hidetoshi; Ghajar, Cyrus M.; Brownfield, Doug; Galgoczy, Roland; Bissell, Mina J.

    2013-01-01

    Collective cell invasion (CCI) through interstitial collagenous extracellular matrix (ECM) is crucial to the initial stages of branching morphogenesis, and a hallmark of tissue repair and dissemination of certain tumors. The collagenous ECM acts as a mechanical barrier against CCI. However, the physical nature of this barrier and how it is overcome by cells remains incompletely understood. To address these questions, we performed theoretical and experimental analysis of mammary epithelial branching morphogenesis in 3D type I collagen (collagen-I) gels. We found that the mechanical resistance of collagen-I is largely due to its elastic rather than its viscous properties. We also identified two strategies utilized by mammary epithelial cells that can independently minimize ECM mechanical resistance during CCI. First, cells adopt a narrow tube-like geometry during invasion, which minimizes the elastic opposition from the ECM as revealed by theoretical modeling of the most frequent invasive shapes and sizes. Second, the stiffness of the collagenous ECM is reduced at invasive fronts due to its degradation by matrix metalloproteinases (MMPs), as indicated by direct measurements of collagen-I microelasticity by atomic force microscopy. Molecular techniques further specified that the membrane-bound MMP14 mediates degradation of collagen-I at invasive fronts. Thus, our findings reveal that MMP14 is necessary to efficiently reduce the physical restraints imposed by collagen-I during branching morphogenesis, and help our overall understanding of how forces are balanced between cells and their surrounding ECM to maintain collective geometry and mechanical stability during CCI. PMID:21993836

  11. Do “trainee-centered ward rounds” help overcome barriers to learning and improve the learning satisfaction of junior doctors in the workplace?

    PubMed Central

    Acharya, Vikas; Reyahi, Amir; Amis, Samuel M; Mansour, Sami

    2015-01-01

    Ward rounds are widely considered an underutilized resource with regard to medical education, and therefore, a project was undertaken to assess if the initiation of “trainee-centered ward rounds” would help improve the confidence, knowledge acquisition, and workplace satisfaction of junior doctors in the clinical environment. Data were collated from junior doctors, registrar grade doctors, and consultants working in the delivery suite at Luton and Dunstable University Hospital in Luton over a 4-week period in March–April 2013. A review of the relevant literature was also undertaken. This pilot study found that despite the reservations around time constraints held by both junior and senior clinicians alike, feedback following the intervention was largely positive. The junior doctors enjoyed having a defined role and responsibility during the ward round and felt they benefited from their senior colleagues’ feedback. Both seniors and junior colleagues agreed that discussing learning objectives prior to commencing the round was beneficial and made the round more learner-orientated; this enabled maximal learner-focused outcomes to be addressed and met. The juniors were generally encouraged to participate more during the round and the consultants endeavored to narrate their decision-making, both were measures that led to greater satisfaction of both parties. This was in keeping with the concept of “Legitimate peripheral participation” as described by Lave and Wenger. Overall, trainee-centered ward rounds did appear to be effective in overcoming some of the traditional barriers to teaching in the ward environment, although further work to formalize and quantify these findings, as well as using greater sample sizes from different hospital departments and the inclusion of a control group, is needed. PMID:26508899

  12. Overcoming psychosocial and developmental barriers to blood and marrow transplantation (BMT) in an adolescent/young adult (AYA) transgender patient with chronic myelogenous leukemia.

    PubMed

    Khazal, Sajad; Abdel-Azim, Hisham; Kapoor, Neena; Mahadeo, Kris M

    2014-11-01

    Adolescents/young adults (AYAs) afflicted with cancer face unique barriers to potentially standard curative therapies, such as blood and marrow transplantation (BMT). Transgender AYAs face additional barriers and there is a dearth of published literature regarding their oncology-related experience. We present the case of an AYA male-to-female (MTF) transgender patient on cross-sex hormone therapy, with a history of Chronic Myelogenous Leukemia (CML) and significant psychosocial barriers, which initially served as a barrier to BMT at two different centers; we modified our standard consent and education process and was able to successfully proceed with BMT and subsequently cure her CML. Despite unique challenges, AYA and transgender patients with significant psychosocial barriers may achieve successful outcomes with BMT. Research is needed regarding guidelines for cross-sex hormone therapy administration for patients undergoing BMT and other issues, which may be unique to the transgender experience.

  13. The Effect of Initiatives to Overcome Language Barriers and Improve Attendance: A Cross-Sectional Analysis of Adherence in an Inner City Chronic Pain Clinic.

    PubMed

    Andreae, Michael H; White, Robert S; Chen, Kelly Yan; Nair, Singh; Hall, Charles; Shaparin, Naum

    2016-07-14

    Language barriers can prevent pain physicians and patients from forming meaningful rapport and drive health care disparities. Non-adherence with scheduled pain clinic appointments deprives patients with chronic pain of needed specialist care.

  14. A Change Agent's Facilitation Process for Overcoming the Barriers of ICT Adoption for Educational Administration--The Case of a Rural-Bangladesh Vocational Institution

    ERIC Educational Resources Information Center

    Khalid, Md. Saifuddin; Nyvang, Tom

    2014-01-01

    The factors influencing the use of information and communication technologies (ICT) as a professional and management tool outside the classroom have received little research attention. The two objectives of this research were: how do stakeholders of educational administration experience the barriers of ICT adoption, and how can they facilitate the…

  15. Tri-membrane nanoparticles produced by combining liposome fusion and a novel patchwork of bicelles to overcome endosomal and nuclear membrane barriers to cargo delivery.

    PubMed

    Yamada, Asako; Mitsueda, Asako; Hasan, Mahadi; Ueda, Miho; Hama, Susumu; Warashina, Shota; Nakamura, Takashi; Harashima, Hideyoshi; Kogure, Kentaro

    2016-03-01

    Membrane fusion is a rational strategy for crossing intracellular membranes that present barriers to liposomal nanocarrier-mediated delivery of plasmid DNA into the nucleus of non-dividing cells, such as dendritic cells. Based on this strategy, we previously developed nanocarriers consisting of a nucleic acid core particle coated with four lipid membranes [Akita, et al., Biomaterials, 2009, 30, 2940-2949]. However, including the endosomal membrane and two nuclear membranes, cells possess three intracellular membranous barriers. Thus, after entering the nucleus, nanoparticles coated with four membranes would still have one lipid membrane remaining, and could impede cargo delivery. Until now, coating a core particle with an odd number of lipid membranes was challenging. To produce nanocarriers with an odd number of lipid membranes, we developed a novel coating method involving lipid nano-discs, also known as bicelles, as a material for packaging DNA in a carrier with an odd number of lipid membranes. In this procedure, bicelles fuse to form an outer coating that resembles a patchwork quilt, which allows the preparation of nanoparticles coated with only three lipid membranes. Moreover, the transfection activity of dendritic cells with these three-membrane nanoparticles was higher than that for nanoparticles coated with four lipid membranes. In summary, we developed novel nanoparticles coated with an odd number of lipid membranes using the novel "patchwork-packaging method" to deliver plasmid DNA into the nucleus via membrane fusion.

  16. Part I: Minicircle vector technology limits DNA size restrictions on ex vivo gene delivery using nanoparticle vectors: Overcoming a translational barrier in neural stem cell therapy.

    PubMed

    Fernandes, Alinda R; Chari, Divya M

    2016-09-28

    Genetically engineered neural stem cell (NSC) transplant populations offer key benefits in regenerative neurology, for release of therapeutic biomolecules in ex vivo gene therapy. NSCs are 'hard-to-transfect' but amenable to 'magnetofection'. Despite the high clinical potential of this approach, the low and transient transfection associated with the large size of therapeutic DNA constructs is a critical barrier to translation. We demonstrate for the first time that DNA minicircles (small DNA vectors encoding essential gene expression components but devoid of a bacterial backbone, thereby reducing construct size versus conventional plasmids) deployed with magnetofection achieve the highest, safe non-viral DNA transfection levels (up to 54%) reported so far for primary NSCs. Minicircle-functionalized magnetic nanoparticle (MNP)-mediated gene delivery also resulted in sustained gene expression for up to four weeks. All daughter cell types of engineered NSCs (neurons, astrocytes and oligodendrocytes) were transfected (in contrast to conventional plasmids which usually yield transfected astrocytes only), offering advantages for targeted cell engineering. In addition to enhancing MNP functionality as gene delivery vectors, minicircle technology provides key benefits from safety/scale up perspectives. Therefore, we consider the proof-of-concept of fusion of technologies used here offers high potential as a clinically translatable genetic modification strategy for cell therapy.

  17. Adaptation to Ephemeral Habitat May Overcome Natural Barriers and Severe Habitat Fragmentation in a Fire-Dependent Species, the Bachman's Sparrow (Peucaea aestivalis)

    PubMed Central

    Cerame, Blain; Cox, James A.; Brumfield, Robb T.; Tucker, James W.; Taylor, Sabrina S.

    2014-01-01

    Bachman's Sparrow (Peucaea aestivalis) is a fire-dependent species that has undergone range-wide population declines in recent decades. We examined genetic diversity in Bachman's Sparrows to determine whether natural barriers have led to distinct population units and to assess the effect of anthropogenic habitat loss and fragmentation. Genetic diversity was examined across the geographic range by genotyping 226 individuals at 18 microsatellite loci and sequencing 48 individuals at mitochondrial and nuclear genes. Multiple analyses consistently demonstrated little genetic structure and high levels of genetic variation, suggesting that populations are panmictic. Based on these genetic data, separate management units/subspecies designations or translocations to promote gene flow among fragmented populations do not appear to be necessary. Panmixia in Bachman's Sparrow may be a consequence of an historical range expansion and retraction. Alternatively, high vagility in Bachman's Sparrow may be an adaptation to the ephemeral, fire-mediated habitat that this species prefers. In recent times, high vagility also appears to have offset inbreeding and loss of genetic diversity in highly fragmented habitat. PMID:25180939

  18. Adaptation to ephemeral habitat may overcome natural barriers and severe habitat fragmentation in a fire-dependent species, the Bachman's Sparrow (Peucaea aestivalis).

    PubMed

    Cerame, Blain; Cox, James A; Brumfield, Robb T; Tucker, James W; Taylor, Sabrina S

    2014-01-01

    Bachman's Sparrow (Peucaea aestivalis) is a fire-dependent species that has undergone range-wide population declines in recent decades. We examined genetic diversity in Bachman's Sparrows to determine whether natural barriers have led to distinct population units and to assess the effect of anthropogenic habitat loss and fragmentation. Genetic diversity was examined across the geographic range by genotyping 226 individuals at 18 microsatellite loci and sequencing 48 individuals at mitochondrial and nuclear genes. Multiple analyses consistently demonstrated little genetic structure and high levels of genetic variation, suggesting that populations are panmictic. Based on these genetic data, separate management units/subspecies designations or translocations to promote gene flow among fragmented populations do not appear to be necessary. Panmixia in Bachman's Sparrow may be a consequence of an historical range expansion and retraction. Alternatively, high vagility in Bachman's Sparrow may be an adaptation to the ephemeral, fire-mediated habitat that this species prefers. In recent times, high vagility also appears to have offset inbreeding and loss of genetic diversity in highly fragmented habitat.

  19. To Grab and To Hold: Cultivating communal goals to overcome cultural and structural barriers in first generation college students' science interest

    PubMed Central

    Allen, Jill M.; Muragishi, Gregg A.; Smith, Jessi L.; Thoman, Dustin B.; Brown, Elizabeth R.

    2015-01-01

    Homogeneity within science limits creativity and discovery, and can feed into a perpetuating cycle of underrepresentation. From enhancing social justice to alleviating health and economic disadvantages, broadening participation in science is imperative. We focus here on first-generation students (FGS) and identify factors which grab and hold science interest among this underrepresented group. Might the culture and norms within science unintentionally limit FGS' participation? We argue that two distinct aspects of communal goals contribute to FGS' underrepresentation at different stages of the STEM pipeline: cultural perceptions of science as uncommunal (little emphasis on prosocial behavior and collaboration) and the uncommunal structure of STEM graduate education and training. Across 2 studies we investigated factors that catch (Study 1) and hold (Study 2) FGS' science interest. In Study 1, we find only when FGS believe that working in science will allow them to fulfill prosocial communal purpose goals are they more intrinsically interested in science. Yet, later in the pipeline science education devalues prosocial communal goals creating a structural mobility barrier among FGS. Study 2 found that FGS generally want to stay close to home instead of relocating to pursue a graduate education. For FGS (versus continuing-generation students), higher prosocial communal goal orientation significantly predicted lower residential mobility. We discuss implications for interventions to counteract the uncommunal science education and training culture to help improve access to FGS and other similarly situated underrepresented populations. PMID:26807431

  20. A critical analysis on the rotation barriers in butane.

    PubMed

    Mo, Yirong

    2010-04-16

    As a textbook prototype for the introduction of steric hindrance in organic chemistry, the elucidation of the butane rotation barriers is fundamental for structural theory, and requires a consistent theoretical model to differentiate the steric and electronic effects. Here we employed the BLW method to probe the electronic (hyperconjugative) interactions. Results show that although there are stronger hyperconjugative interactions in the staggered anti and gauche conformers than the eclipsed structures, the energy curve and barriers are dominated by the steric repulsion.

  1. Overcoming language barriers when teaching interprofessional groups.

    PubMed

    Welsh, Jeanette

    2012-10-01

    The author of this article undertook a small qualitative study of the best way to prepare unscheduled care staff for team-based delivery of patient care. The study was intended to highlight problems in interprofessional training courses so that guidelines for the delivery of such courses can be developed. The findings show that trainers cannot assume that all participants in training courses understand the terminology used. This article discusses this finding further.

  2. Photon localization barrier can be overcome

    NASA Astrophysics Data System (ADS)

    Saari, P.; Menert, M.; Valtna, H.

    2005-02-01

    In contradistinction to a widespread belief that the spatial localization of photons is restricted by a power-law falloff of the photon energy density, Bialynicki-Birula [Phys. Rev. Lett. 80 (1998) 5247] has proved that any stronger - up to an almost exponential - falloff is allowed. We are showing that for certain specifically designed cylindrical one-photon states the localization is even better in lateral directions. If the photon state is built from the so-called focus wave mode, the falloff in the waist cross-section plane turns out to be quadratically exponential (Gaussian) and such strong localization persists in the course of propagation.

  3. Childhood lymphoedema and 'Lymphaletics': overcoming barriers.

    PubMed

    Todd, Marie

    2016-07-14

    Primary lymphoedema is a complex condition that causes tissue swelling, usually in one or more of the limbs, but lymphatic drainage of the head, trunk or deeper organs may also be affected. It can manifest in swelling at any time from birth meaning there are a number of children affected by this condition. While it is rare in childhood there are too few professionals experienced in diagnosis and treatment, which results in delays in identification and referral to appropriate services for diagnosis and treatment. The Children's Lymphoedema Special Interest Group (CLSIG) was formed in 2010 by a group of lymphoedema specialists in a bid to raise awareness, improve service provision, and enhance practitioner knowledge. One of the aims of the group was to deliver a 'fun day' (Lymphaletics) for children with lymphoedema and their families to encourage physical activity and social interaction with children who have similar problems, and to provide a source of parent-to-parent support. This article discusses the issues for children and their families, and the aims and format of the event.

  4. Overcoming Barriers to Classroom Technology Integration

    ERIC Educational Resources Information Center

    Kelly, Daniel P.

    2015-01-01

    Technology-savvy teachers are often the "go to" staff members in schools for their colleagues' technology issues. These teachers are seen as leaders within their schools with respect to technology and often do not understand their peers' difficulties when bringing technology into the classroom. Understanding both the reasons teachers may…

  5. Overcoming the Adoption Barrier to Electric Flight

    NASA Technical Reports Server (NTRS)

    Borer, Nicholas K.; Nickol, Craig L.; Jones, Frank P.; Yasky, Richard J.; Woodham, Kurt; Fell, Jared S.; Litherland, Brandon L.; Loyselle, Patricia L.; Provenza, Andrew J.; Kohlman, Lee W.; Samuel, Aamod G.

    2016-01-01

    Electrically-powered aircraft can enable dramatic increases in efficiency and reliability, reduced emissions, and reduced noise as compared to today's combustion-powered aircraft. This paper describes a novel flight demonstration concept that will enable the benefits of electric propulsion, while keeping the extraordinary convenience and utility of common fuels available at today's airports. A critical gap in airborne electric propulsion research is addressed by accommodating adoption at the integrated aircraft-airport systems level, using a confluence of innovative but proven concepts and technologies in power generation and electricity storage that need to reside only on the airframe. Technical discriminators of this demonstrator concept include (1) a novel, high-efficiency power system that utilizes advanced solid oxide fuel cells originally developed for ultra-long-endurance aircraft, coupled with (2) a high-efficiency, high-power electric propulsion system selected from mature products to reduce technical risk, assembled into (3) a modern, high-performance demonstration platform to provide useful and compelling data, both for the targeted early adopters and the eventual commercial market.

  6. Overcoming Barriers to Shared Decision Making

    MedlinePlus

    ... second opinion . Learn more: About Advanced Heart Failure Recognition and Knowing Your Options Planning Ahead Communicating With ... Healthcare Team Help for Caregivers Advanced Heart Failure Recognition and Knowing Your Options Planning Ahead Communicating with ...

  7. Overcoming Learning Barriers through Knowledge Management

    ERIC Educational Resources Information Center

    Dror, Itiel E.; Makany, Tamas; Kemp, Jonathan

    2011-01-01

    The ability to learn highly depends on how knowledge is managed. Specifically, different techniques for note-taking utilize different cognitive processes and strategies. In this paper, we compared dyslexic and control participants when using linear and non-linear note-taking. All our participants were professionals working in the banking and…

  8. Overcoming the Cutaneous Barrier with Microemulsions

    PubMed Central

    Lopes, Luciana B.

    2014-01-01

    Microemulsions are fluid and isotropic formulations that have been widely studied as delivery systems for a variety of routes, including the skin. In spite of what the name suggests, microemulsions are nanocarriers, and their use as topical delivery systems derives from their multiple advantages compared to other dermatological formulations, such as ease of preparation, thermodynamic stability and penetration-enhancing properties. Composition, charge and internal structure have been reported as determinant factors for the modulation of drug release and cutaneous and transdermal transport. This manuscript aims at reviewing how these and other characteristics affect delivery and make microemulsions appealing for topical and transdermal administration, as well as how they can be modulated during the formulation design to improve the potential and efficacy of the final system. PMID:24590260

  9. Overcoming the Uncertainty Barrier to Adaptation

    EPA Pesticide Factsheets

    The second in a three-part webinar series about climate change adaptation for state and local governments, this webinar addressed the challenge of planning for climate change in the face of uncertainty.

  10. Crystal structures of three sterically congested disilanes

    PubMed Central

    Pichaandi, Kothanda Rama

    2017-01-01

    In the three sterically congested silanes, C24H38Si2 (1) (1,1,2,2-tetra­isopropyl-1,2-di­phenyl­disilane), C24H34Br4Si2 (2) [1,1,2,2-tetra­kis­(2-bromo­propan-2-yl)-1,2-di­phenyl­disilane] and C32H38Si2 (3) (1,2-di-tert-butyl-1,1,2,2-tetra­phenyl­disilane), the Si—Si bond length is shortest in (1) and longest in (2), with (3) having an inter­mediate value, which parallels the increasing steric congestion. A comparison of the two isopropyl derivatives, (1 and 2), shows a significant increase in the Si—C(ipso) distance with the introduction of bromine. Also, in the brominated compound 2, attractive inter­molecular Br⋯Br inter­actions exist with Br⋯Br separations ca 0.52 Å shorter than the sum of the van der Waals radii. In compound 2, one of the bromo­isopropyl groups is rotationally disordered in an 0.8812 (9):0.1188 (9) ratio. Compound 3 exhibits ‘whole mol­ecule’ disorder in a 0.9645 (7):0.0355 (7) ratio with the Si—Si bonds in the two components making an angle of ca 66°. PMID:28316829

  11. Steric interactions between two grafted polymer brushes

    NASA Astrophysics Data System (ADS)

    Ruckenstein, Eli; Li, Buqiang

    1997-07-01

    A lattice model and a generator-matrix method are employed to calculate the interaction force profile between two grafted polymer brushes. The correlation between neighboring bonds and the interdigitation between the two brushes are taken into account. The calculations show that the effect of incorporating the bond correlations is equivalent to an increase in the value of the polymer-solvent interaction parameter when the bond correlations are ignored. The interdigitation between the two brushes decreases the free energy of the system and consequently results in a smaller steric repulsion. A complete interdigitation occurs at a separation close to half the separation between the two plates for which the interaction force is zero. The model is compared with the experimental interaction force profiles for ten systems which involve poly(2-vinylpyridine)-polyisoprene (PVP-PI), poly(2-vinylpyridine)-polystyrene (PVP-PS) block copolymers as well as end-functionalized polystyrenes (PS-X). For most of the systems, the theoretical predictions are in good agreement with experiment. In addition, the present results are compared with the equations proposed by de Gennes, based on the assumption of a step distribution function for the segment density, and by Milner et al., based on the parabolic distribution of the segment density. Both equations neglected interdigitation. It is shown in this paper that the interdigitation is not negligible and that it can decrease by an order of magnitude the repulsive force.

  12. From information theory to quantitative description of steric effects.

    PubMed

    Alipour, Mojtaba; Safari, Zahra

    2016-07-21

    Immense efforts have been made in the literature to apply the information theory descriptors for investigating the electronic structure theory of various systems. In the present study, the information theoretic quantities, such as Fisher information, Shannon entropy, Onicescu information energy, and Ghosh-Berkowitz-Parr entropy, have been used to present a quantitative description for one of the most widely used concepts in chemistry, namely the steric effects. Taking the experimental steric scales for the different compounds as benchmark sets, there are reasonable linear relationships between the experimental scales of the steric effects and theoretical values of steric energies calculated from information theory functionals. Perusing the results obtained from the information theoretic quantities with the two representations of electron density and shape function, the Shannon entropy has the best performance for the purpose. On the one hand, the usefulness of considering the contributions of functional groups steric energies and geometries, and on the other hand, dissecting the effects of both global and local information measures simultaneously have also been explored. Furthermore, the utility of the information functionals for the description of steric effects in several chemical transformations, such as electrophilic and nucleophilic reactions and host-guest chemistry, has been analyzed. The functionals of information theory correlate remarkably with the stability of systems and experimental scales. Overall, these findings show that the information theoretic quantities can be introduced as quantitative measures of steric effects and provide further evidences of the quality of information theory toward helping theoreticians and experimentalists to interpret different problems in real systems.

  13. Steric stabilization of microspheres with grafted polyethylene oxide reduces phagocytosis by rat Kupffer cells in vitro.

    PubMed

    Harper, G R; Davies, M C; Davis, S S; Tadros, T F; Taylor, D C; Irving, M P; Waters, J A

    1991-09-01

    Sterically stabilized polyethylene oxide-polystyrene copolymer microspheres, (PS-PEO) and charge stabilized polystyrene (PS) microspheres of similar size (1 micron) were prepared in order to compare their uptake by cultured rat Kupffer cells isolated by centrifugal elutriation. The uptake of the sterically stabilized particles was found to be much less than that for the charge stabilized control. The uptake of microspheres stabilized with covalently grafted PEO was lower or equivalent to that of control microspheres stabilized by the adsorption of the non-ionic PEO-polypropylene oxide (PPO-PEO) surfactant Poloxamer 238 or Methoxy-PEO. Phagocytic uptake by Kupffer cells at low and body temperature (8 degrees C and 37 degrees C) demonstrated that PS-PEO particles showed both low adherence and low metabolic uptake. The adsorption of PEO, as Poloxamer 238, to particles with covalently attached or grafted PEO resulted in a synergistic reduction in uptake that was greater than the individual effects of grafting and adsorption alone (P less than or equal to 0.001). It is suggested that this combination produces a more effective steric barrier on the particle surface with the Poloxamer adsorbing to the surface between the grafted PEO chains. The relevance to drug targeting/carrier systems is discussed.

  14. Density functional steric analysis of linear and branched alkanes.

    PubMed

    Ess, Daniel H; Liu, Shubin; De Proft, Frank

    2010-12-16

    Branched alkane hydrocarbons are thermodynamically more stable than straight-chain linear alkanes. This thermodynamic stability is also manifest in alkane bond separation energies. To understand the physical differences between branched and linear alkanes, we have utilized a novel density functional theory (DFT) definition of steric energy based on the Weizäcker kinetic energy. Using the M06-2X functional, the total DFT energy was partitioned into a steric energy term (E(s)[ρ]), an electrostatic energy term (E(e)[ρ]), and a fermionic quantum energy term (E(q)[ρ]). This analysis revealed that branched alkanes have less (destabilizing) DFT steric energy than linear alkanes. The lower steric energy of branched alkanes is mitigated by an equal and opposite quantum energy term that contains the Pauli component of the kinetic energy and exchange-correlation energy. Because the steric and quantum energy terms cancel, this leaves the electrostatic energy term that favors alkane branching. Electrostatic effects, combined with correlation energy, explains why branched alkanes are more stable than linear alkanes.

  15. Density Functional Steric Analysis of Linear and Branched Alkanes

    SciTech Connect

    Ess, Daniel H.; Liu, Shubin; De Proft, Frank

    2010-11-18

    Branched alkane hydrocarbons are thermodynamically more stable than straight-chain linear alkanes. This thermodynamic stability is also manifest in alkane bond separation energies. To understand the physical differences between branched and linear alkanes, we have utilized a novel density functional theory (DFT) definition of steric energy based on the Weizäcker kinetic energy. Using the M06-2X functional, the total DFT energy was partitioned into a steric energy term (Ee[[ρ]), an electrostatic energy term (Ee[ρ]), and a fermionic quantum energy term (Eq[[ρ]). This analysis revealed that branched alkanes have less (destabilizing) DFT steric energy than linear alkanes. The lower steric energy of branched alkanes is mitigated by an equal and opposite quantum energy term that contains the Pauli component of the kinetic energy and exchange-correlation energy. Because the steric and quantum energy terms cancel, this leaves the electrostatic energy term that favors alkane branching. Electrostatic effects, combined with correlation energy, explains why branched alkanes are more stable than linear alkanes.

  16. Overcoming breastfeeding problems

    MedlinePlus

    Plugged milk ducts; Nipple soreness when breastfeeding; Breastfeeding - overcoming problems; Let-down reflex ... Breastfeeding (nursing) your baby can be a good experience for both the mother and the baby. It ...

  17. Overcoming recruitment barriers revealed high readiness to participate and low dropout rate among people with schizophrenia in a randomized controlled trial testing the effect of a Guided Self-Determination intervention

    PubMed Central

    2014-01-01

    Background Recruitment is one of the most serious challenges in performing randomized controlled trials. Often clinical trials with participants diagnosed with schizophrenia are terminated prematurely because of recruitment challenges resulting in a considerable waste of resources in the form of time, funding, and the participants’ efforts. Dropout rates in schizophrenia trials are also high. Recruitment challenges are often due to patients not wanting to participate in research but can also be due to clinicians’ concerns regarding individuals diagnosed with schizophrenia as participants in research. This paper reports how overcoming recruitment challenges not related to patients revealed high readiness to take part and low dropout rates in a one year long randomized controlled trial testing Guided Self-Determination (GSD) among outpatients with schizophrenia receiving treatment in Assertive Outreach Teams in the northern part of Denmark. Methods GSD is a shared decision-making and mutual problem-solving method using reflection sheets, which was developed in diabetes care and adjusted for this study and utilized by patients with schizophrenia. Descriptive data on strategies to overcome recruitment challenges were derived from notes and observations made during the randomized controlled trial testing of GSD in six outpatient teams. Results Three types of recruitment challenges not related to patients were identified and met during the trial: 1) organizational challenges, 2) challenges with finding eligible participants and 3) challenges with having professionals invite patients to participate. These challenges were overcome through: 1) extension of time, 2) expansion of the clinical recruitment area and 3) encouragement of professionals to invite patients to the study. Through overcoming these challenges, we identified a remarkably high patient-readiness to take part (101 of 120 asked accepted) and a low dropout rate (8%). Conclusion Distinction between

  18. Sterically shielded diboron-containing metallocene olefin polymerization catalysts

    DOEpatents

    Marks, Tobin J.; Ja, Li; Yang, Xinmin

    1995-09-05

    A non-coordinating anion, preferably containing a sterically shielded diboron hydride, if combined with a cyclopenta-dienyl-substituted metallocene cation component, such as a zirconocene metallocene, is a useful olefin polymerization catalyst component. The anion preferably has the formula ##STR1## where R is branched lower alkyl, such as t-butyl.

  19. Origin of anomeric effect: A density functional steric analysis

    SciTech Connect

    Huang, Ying; Zhong, Ai-Guo; Yang, Qinsong; Liu, Shubin

    2011-01-01

    The anomeric effect (the tendency of heteroatomic substituents adjacent to a heteroatom within the cyclohexane ring to prefer the axial orientation instead of the sterically less hindered equatorial position) is traditionally explained through either the dipole moment repulsion or the hyperconjugation effect. In this work, by employing our recent work in density functional steric analysis, we provide a novel two-component explanation, which is consistent with the common belief in chemistry that the effect has a stereoelectronic origin. With α-D-glucopyranose as the prototype, we systematically explore its conformational space and generate 32 isomers, leading to a total of 80 axial–equatorial conformation pairs. The energy difference analysis of these pairs shows that while statistically speaking the tendency is valid, the anomeric effect is not always true and can be violated. Three energy components, exchange–correlation, classical electrostatic, and density functional steric, are found to be directly proportional to the total energy difference between axial and equatorial isomers. We also found that the total dipole moment change, not the hyperconjugation effect, is a reasonable indicator of the total energy difference. However, all these correlations alone are not strong enough to provide a compellingly convincing explanation for the general validity of the effect. With the help of strong correlations between energy components, an explanation with two energy components, steric and electrostatic, was proposed in this work. We show that the axial–equatorial energy difference in general, with the anomeric effect as a special case, is dictated by two factors of the stereoelectronic origin, steric hindrance and classical electrostaticinteractions, synchronously working together. Another explanation in terms of exchange–correlation and electrostaticinteractions has also been obtained in this work.

  20. Steric Pressure among Membrane-Bound Polymers Opposes Lipid Phase Separation.

    PubMed

    Imam, Zachary I; Kenyon, Laura E; Carrillo, Adelita; Espinoza, Isai; Nagib, Fatema; Stachowiak, Jeanne C

    2016-04-19

    Lipid rafts are thought to be key organizers of membrane-protein complexes in cells. Many proteins that interact with rafts have bulky polymeric components such as intrinsically disordered protein domains and polysaccharide chains. Therefore, understanding the interaction between membrane domains and membrane-bound polymers provides insights into the roles rafts play in cells. Multiple studies have demonstrated that high concentrations of membrane-bound polymeric domains create significant lateral steric pressure at membrane surfaces. Furthermore, our recent work has shown that lateral steric pressure at membrane surfaces opposes the assembly of membrane domains. Building on these findings, here we report that membrane-bound polymers are potent suppressors of membrane phase separation, which can destabilize lipid domains with substantially greater efficiency than globular domains such as membrane-bound proteins. Specifically, we created giant vesicles with a ternary lipid composition, which separated into coexisting liquid ordered and disordered phases. Lipids with saturated tails and poly(ethylene glycol) (PEG) chains conjugated to their head groups were included at increasing molar concentrations. When these lipids were sparse on the membrane surface they partitioned to the liquid ordered phase. However, as they became more concentrated, the fraction of GUVs that were phase-separated decreased dramatically, ultimately yielding a population of homogeneous membrane vesicles. Experiments and physical modeling using compositions of increasing PEG molecular weight and lipid miscibility phase transition temperature demonstrate that longer polymers are the most efficient suppressors of membrane phase separation when the energetic barrier to lipid mixing is low. In contrast, as the miscibility transition temperature increases, longer polymers are more readily driven out of domains by the increased steric pressure. Therefore, the concentration of shorter polymers required

  1. Overcoming the Polyester Image.

    ERIC Educational Resources Information Center

    Regan, Dorothy

    1988-01-01

    Urges community colleges to overcome their image problem by documenting the colleges' impact on their communities. Suggests ways to determine what data should be collected, how to collect the information, and how it can be used to empower faculty, staff, and alumni to change the institution's image. (DMM)

  2. Steric hindrances create a discrete linear Dy4 complex exhibiting SMM behaviour.

    PubMed

    Lin, Shuang-Yan; Zhao, Lang; Ke, Hongshan; Guo, Yun-Nan; Tang, Jinkui; Guo, Yang; Dou, Jianmin

    2012-03-21

    Two linear tetranuclear lanthanide complexes of general formula [Ln(4)(L)(2)(C(6)H(5)COO)(12)(MeOH)(4)], where HL = 2,6-bis((furan-2-ylmethylimino)methyl)-4-methylphenol, () and Ln(III) = Dy(III) (1) and Gd(III) (2), have been synthesized and characterized. The crystal structural analysis demonstrates that two Schiff-base ligands inhibit the growth of benzoate bridged 1D chains, leading to the isolation of discrete tetranuclear complexes due to their steric hindrances. Every Ln(III) ion is coordinated by eight donor atoms in a distorted bicapped trigonal-prismatic arrangement. Alternating current (ac) susceptibility measurements of complex 1 reveal a frequency- and temperature-dependent out-of-phase signal under zero dc field, typical of single-molecule magnet (SMM) behaviour with an anisotropic barrier Δ(eff) = 17.2 K.

  3. Computational design of faster rotating second-generation light-driven molecular motors by control of steric effects.

    PubMed

    Oruganti, Baswanth; Fang, Changfeng; Durbeej, Bo

    2015-09-07

    We report a systematic computational investigation of the possibility to accelerate the rate-limiting thermal isomerizations of the rotary cycles of synthetic light-driven overcrowded alkene-based molecular motors through modulation of steric interactions. Choosing as a reference system a second-generation motor known to accomplish rotary motion in the MHz regime and using density functional theory methods, we propose a three-step mechanism for the thermal isomerizations of this motor and show that variation of the steric bulkiness of the substituent at the stereocenter can reduce the (already small) free-energy barrier of the rate-determining step by a further 15-17 kJ mol(-1). This finding holds promise for future motors of this kind to reach beyond the MHz regime. Furthermore, we demonstrate and explain why one particular step is kinetically favored by decreasing and another step is kinetically favored by increasing the steric bulkiness of this substituent, and identify a possible back reaction capable of impeding the rotary rate.

  4. Practical catalytic method for synthesis of sterically hindered anilines.

    PubMed

    Mailig, Melrose; Rucker, Richard P; Lalic, Gojko

    2015-07-14

    A practical catalytic method for the synthesis of sterically hindered anilines is described. The amination of aryl and heteroaryl boronic esters is accomplished using a catalyst prepared in situ from commercially available and air-stable copper(i) triflate and diphosphine ligand. For the first time, the method can be applied to the synthesis of both secondary and tertiary anilines in the presence of a wide range of functional groups. Esters, aldehydes, alcohols, aryl halides, ketones, nitriles, and nitro arenes are all compatible with the reaction conditions. Finally, even the most sterically hindered anilines can be successfully prepared under mild reaction conditions. Overall, the new method addresses significant practical limitations of a transformation previously developed in our lab, and provides a valuable complement to the existing methods for the synthesis of anilines.

  5. Interactions of triazine herbicides with biochar: Steric and electronic effects.

    PubMed

    Xiao, Feng; Pignatello, Joseph J

    2015-09-01

    We studied the adsorption of triazine herbicides and several reference heteroaromatic amines from water onto a temperature series of hardwood biochars (300-700 °C, labeled B300-B700). Adsorption on biochars correlated poorly with pyrolysis temperature, H/C, O/C, mean minimum fused ring size, surface area (N2 or CO2), microporosity, and mesoporosity, but correlated well with a weighted sum of microporosity and mesoporosity. Steric effects were evident by the negative influence of solute molecular volume on adsorption rate. For a given compound, adsorption rate maximized for the biochar with the greatest mesoporosity-to-total-porosity ratio, suggesting that mesopores are important for facilitating diffusion into pore networks. The cationic forms of amines adsorb more slowly than the neutral forms. To further probe steric and electronic effects, adsorption on a biochar (B400) was compared to adsorption on graphite-a nonporous reference material with an unhindered, unfunctionalized graphene surface-and in comparison with reference compounds (benzene, naphthalene, pyridine, quinoline and 1,3-triazine). Relative to benzene, the surface area-normalized adsorption of the triazine herbicides was disfavored on B400 (favored on graphite) by 11-19 kJ/mol, depending on concentration. It is estimated that steric suppression of B400 adsorption comprises 6.2 kJ/mol of this difference, the remainder being the difference in polar electronic effects. Based on the behavior of the reference amines, the difference in polar effects is dominated by π-π electron donor-acceptor (EDA) interactions with sites on polyaromatic surfaces, which are more electropositive and/or more abundant on graphite. Overall, our results show that mesoporosity is critical, that adsorption rate is a function of solute molecular size and charge, that steric bulk in the solute suppresses equilibrium adsorption, and that π-π EDA forces play a role in triazine polar interactions with biochar.

  6. Rotational, steric, and coriolis effects on the F + HCl --> HF + Cl reaction on the 1(2)A' ground-state surface.

    PubMed

    Defazio, Paolo; Petrongolo, Carlo

    2009-04-23

    We present a quantum study of the reaction F((2)P) + HCl(X(1)Sigma(+)) --> HF(X(1)Sigma(+)) + Cl((2)P) on a recently computed 1(2)A' ground-state surface, considering HCl in the ground vibrational state, with up to 16 rotational quanta j(0). We employ the real wavepacket (WP) and flux methods for calculating coupled-channel (CC) and centrifugal-sudden (CS) initial-state probabilities up to J = 80 and 140, respectively. We also report CC and CS ground-state cross sections and CS excited-state cross sections and discuss the dynamics analyzing WP time evolutions. The HCl rotation highly enhances reaction probabilities and cross sections, as it was previously found for probabilities at J Steric effects favor indeed the overcoming of the potential barrier and a linearly dominated mechanism. Attractive Coriolis couplings favor instead the energy flow from the HCl rotation to the F-H---Cl reactive vibration. WP snapshots confirm and explain the HCl rotational effects, because the density into the nearly collinear F-H---Cl product channel increases remarkably with j(0). Finally, our CS rate constant is underestimated with respect to the experiment, pointing out the need of more accurate multisurface and CC calculations.

  7. Ion channel gates: comparative analysis of energy barriers.

    PubMed

    Tai, Kaihsu; Haider, Shozeb; Grottesi, Alessandro; Sansom, Mark S P

    2009-04-01

    The energetic profile of an ion translated along the axis of an ion channel should reveal whether the structure corresponds to a functionally open or closed state of the channel. In this study, we explore the combined use of Poisson-Boltzmann electrostatic calculations and evaluation of van der Waals interactions between ion and pore to provide an initial appraisal of the gating state of a channel. This approach is exemplified by its application to the bacterial inward rectifier potassium channel KirBac3.1, where it reveals the closed gate to be formed by a ring of leucine (L124) side chains. We have extended this analysis to a comparative survey of gating profiles, including model hydrophobic nanopores, the nicotinic acetylcholine receptor, and a number of potassium channel structures and models. This enables us to identify three gating regimes, and to show the limitation of this computationally inexpensive method. For a (closed) gate radius of 0.4 nm < R < 0.8 nm, a hydrophobic gate may be present. For a gate radius of 0.2 nm < R < 0.4 nm, both electrostatic and van der Waals interactions will contribute to the barrier height. Below R = 0.2 nm, repulsive van der Waals interactions are likely to dominate, resulting in a sterically occluded gate. In general, the method is more useful when the channel is wider; for narrower channels, the flexibility of the protein may allow otherwise-unsurmountable energetic barriers to be overcome.

  8. Computational study of the effects of steric hindrance on amide bond cleavage.

    PubMed

    Matsubara, Toshiaki; Ueta, Chikako

    2014-09-25

    The reaction mechanism of amide bond cleavages of the 2,2,6,6-tetramethylpiperidine derivatives, which proceeds in methanol solvent under mild conditions, is examined by the density functional method (B3LYP) using a model substrate. We performed the calculations to clarify the reason why the amide bond is readily broken in the present system, on the basis of an experimentally proposed "proton switching pathway" that is different from the generally known mechanisms. As a result, it was found that the stepwise decomposition of the amide bond by the "proton switching pathway" significantly lowers the energy barrier. The delocalization of the π electron in the -C(═O)-N< part is hindered by the steric effect of the four Me groups of the piperidine so that the acetyl group can easily rotate around the C-N axis and then the α-H migrates to the amide N. The subsequent amide bond dissociation, which is thought to be a rate-determining step in the experiment, was very facile. The reaction is completed by the addition of methanol to the formed ketene. Both the energy barriers of the α-H migration to the amide N and the methanol addition to ketene are largely decreased by the mediation of methanol solvent molecules. The rate-determining step of the entire reaction was found to be the α-H migration.

  9. Large steric effect in the substitution reaction of amines with phosphoimidazolide-activated nucleosides

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Stronach, M. W.; Ketner, R. J.; Hurley, T. B.

    1995-01-01

    Aliphatic amines react with phosphoimidazolide-activated derivatives of guanosine and cytidine (ImpN) by replacing the imidazole group. The kinetics of reaction of guanosine 5'-phospho-2-methylimidazolide (2-MeImpG) with glycine ethyl ester, glycinamide, 2-methoxyethylamine, n-butylamine, morpholine, dimethylamine (Me2NH), ethylmethylamine (EtNHMe), diethylamine (Et2NH), pyrrolidine, and piperidine were determined in water at 37 degrees C. With primary amines, a plot of the logarithm of the rate constant for attack by the amine on the protonated substrate, log kSH(A), versus the pKa of the amine exhibits a good linear correlation with a Bronsted slope, beta nuc = 0.48. Most of the secondary amines tested react with slightly higher reactivity than primary amines of similar pKa. Interestingly, some secondary amines show substantially lower reactivity than might be expected: EtNHMe reacts about eight times, and Et2NH at least 100 times, more slowly than Me2NH although all three amines are of similar basicity. For comparison, the kinetics of reaction of guanosine 5'-phosphoimidazolide (ImpG) and cytidine 5'-phosphoimidazolide (ImpC) were determined with Me2NH, EtNHMe, and Et2NH, and similar results were obtained. These results establish that the increased steric hindrance observed with the successive addition of ethyl groups are not due to any special steric requirements imposed by the guanosine or the methyl on the 2-methylimidazole leaving group of 2-MeImpG. It is concluded that addition of ethyl and, perhaps, groups larger than ethyl dramatically increases the kinetic barrier for addition of aliphatic secondary amines to the P-N bond of ImpN. This study supports the observation that the primary amino groups on the natural polyamines are at least 2 orders of magnitude more reactive than the secondary amino groups in the reaction with ImpN.

  10. Aluminum foils: the contrasting characters of hyperconjugation and steric repulsion in aluminum dimetallocenes.

    PubMed

    Compaan, Katherine R; Wilke, Jeremiah J; Schaefer, Henry F

    2011-08-31

    The novel sandwich complex Cp2*Al2I2, which was recently synthesized by Minasian and Arnold, has been characterized using ab initio and density functional methods. A large family of related compounds was also investigated. Although a few Al(II)–Al(II) bonds are known, this is the first such bond to be supported by Cp-type ligands. In addition, in the remarkable Cp4*Al4 synthesis by Roesky, Cp2*Al2I2 is the Al(II) intermediate; Cp4*Al4 is important as a precursor to novel organoaluminum species. Halogen and ligand effects on the Al–Al bond in Cp2*Al2I2 were systematically explored by studying a series of 20 Cp2*Al2I2 derivatives using density functional theory with relativistic basis sets for the halogens. Comparison was made with the focal point treatment, which uses extrapolation to estimate the full configuration interaction and complete basis set limit energy. Torsional potential energy curves, natural population analyses, and enthalpies of hydrogenation were computed. Using the focal point approach, torsional barriers were computed with 0.05 kcal mol(–1) uncertainty. The interplay of steric and electronic effects on the torsional potential energy curves, enthalpies of dehydrogenation reactions, and geometries is discussed. In species with small ligands (R = H, Me), hyperconjugative effects determine the torsional landscape, whereas steric repulsions dominate in species with Cp* alkyl ligands. Species with Cp ligands represent an intermediate case, thus providing insight into how ligands modulate the structures and properties of small metal clusters.

  11. Barriers to improvements in energy efficiency

    SciTech Connect

    Reddy, A.K.N.

    1991-10-01

    To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the ``barriers`` literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

  12. Barriers to improvements in energy efficiency

    SciTech Connect

    Reddy, A.K.N.

    1991-10-01

    To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the barriers'' literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

  13. Retinal Photoisomerization in Rhodopsin: Electrostatic and Steric Catalysis

    SciTech Connect

    Tomasello, Gaia; Altoe, Piero; Stenta, Marco; Olaso-Gonzalez, Gloria; Garavelli, Marco; Orlandi, Giorgio

    2007-12-26

    Excited state QM(CASPT2//CASSCF)/MM(GAFF) calculations, by our recently developed code COBRAMM (Computations at Bologna Relating Ab-initio and Molecular Mechanic Methods), were carried out in rhodopsin to investigate on the steric and electrostatic effects in retinal photoisomerization catalysis due to the {beta}-ionone ring and glutammate 181 (GLU 181), respectively. The excited state photoisomerization channel has been mapped and a new christallographyc structure (2.2 Aa resolution) has been used for this purpose. Two different set-ups have been used to evaluate the electrostatic effects of GLU 181 (which is very close to the central double bond of the chromophore): the first with a neutral GLU 181 (as commonly accepted), the second with a negatively charged (i.e. deprotonated) GLU 181 (as very recent experimental findings seem to suggest). On the other hand, {beta}-ionone ring steric effects were evaluated by calculating the photoisomerization path of a modified chromophore, where the ring double bond has been saturated. Spectroscopic properties were calculated and compared with the available experimental data.

  14. Psychological Barriers to Behavior Change

    PubMed Central

    Olson, James M.

    1992-01-01

    Adopting a healthy lifestyle often requires changing patterns of behavior. This article describes three categories of psychological barriers to behavior change: those that prevent the admission of a problem, those that interfere with initial attempts to change behavior, and those that make long-term change difficult. Strategies are identified that family physicians can use to overcome the barriers. PMID:21221258

  15. Steric-electronic effects in malarial peptides inducing sterile immunity

    SciTech Connect

    Moreno-Vranich, Armando; Patarroyo, Manuel E.

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer Is it evident that the residues position are relevant regarding of {phi} angular value. Black-Right-Pointing-Pointer The geometry considered for detailing the alterations undergone by HABPs. Black-Right-Pointing-Pointer The inter planar interactions ruled by clashes between the atoms making them up. -- Abstract: Conserved Plasmodium falciparum high activity binding peptides' (HABPs) most relevant proteins involved in malaria parasite invasion are immunologically silent; critical binding residues must therefore be specifically replaced to render them highly immunogenic and protection-inducing. Such changes have a tremendous impact on these peptides' steric-electronic effects, such as modifications to peptide length peptide bonds and electronic orbitals' disposition, to allow a better fit into immune system MHCII molecules and better interaction with the TCR which might account for the final immunological outcome.

  16. Steric effects and preferential interactions in supercritical carbon dioxide

    SciTech Connect

    Saquing, C.D.; Lucien, F.P.; Foster, N.R

    1998-10-01

    Solubility data are presented for a mixture of o-hydroxybenzoic acid (o-HBA) and m-HBA in supercritical CO{sub 2} doped with 3.5 mol% methanol. The data were measured at 318 and 328 K and for pressures in the range of 101--201 bar. Some new data for the solubility of pure m-HBA in methanol-doped supercritical CO{sub 2} are also presented. The solubilities of the HBA isomers are enhanced considerably with the addition of methanol to supercritical CO{sub 2}. However, the solubility enhancement is strongly affected by the spatial arrangement of their functional groups (steric effect). There appears to be preferential interaction between the solutes and the cosolvent in the quaternary system, and this phenomenon is consistent with thermodynamic modeling of the system.

  17. Steric hindrance in a MnSalen expoxidation catalyst

    SciTech Connect

    Jun, K.W.; Wilson, R.B. Jr.; Asaro, M.F.

    1995-12-31

    Many transition metal epoxidation catalysts use porphyrin type ligands, as biomimetic models for the well-studied monooxygenase, Cyt P-450. Recently, non-porphyrin systems based on the Salen ligand have received attention, because high e.e. values are reported using chiral Salen ligands. These systems have yet to be rendered generally practical, however, because the catalyst lifetimes are very short and the turnover numbers low. The original Mn(III) Salen epoxidation catalysts became inactive within 1 h, showing only 5 to 10 turnovers. The modified, chiral Mn(III) Salen complexes show similarly low turnovers. The principal decomposition routes of the MnSalen epoxidation catalysts are not clear. The purpose of the present study is to determine whether incorporation of extreme steric hindrance into the Salen ligand could be used to increase the lifetime of the Mn(III) Salen epoxidation catalysts.

  18. Formation and collapse of gels of sterically stabilized colloidal particles

    NASA Astrophysics Data System (ADS)

    Weeks, James R.; van Duijneveldt, Jeroen S.; Vincent, Brian

    2000-11-01

    Colloidal silica spheres (diameter 88 nm) with a thick steric stabilization layer of polystyrene (PS; Mw = 26 600 g mol-1) were prepared. In cyclohexane, a marginal solvent for PS, particle aggregation and gelation were observed on lowering the temperature. Near the gelation temperature and at particle concentrations of a few per cent by weight, the gels were sufficiently weak to slowly compact under gravity. On quenching to slightly lower temperatures, the gels still settled, but the top of the sediment did not become flat, as is usually the case. This seems to be related to an unusual mechanism for gel compaction, which starts by forming a more dense structure at the top of the sample. It is proposed that this is related to the entangled polymer chains on neighbouring particles resisting substantial rearrangement of the local structure. The transient gelation phenomenon, observed previously for mixtures of colloid and non-adsorbing polymer, has so far not been observed for our system.

  19. Sterically stabilized water based magnetic fluids: Synthesis, structure and properties

    NASA Astrophysics Data System (ADS)

    Bica, Doina; Vékás, Ladislau; Avdeev, Mikhail V.; Marinică, Oana; Socoliuc, Vlad; Bălăsoiu, Maria; Garamus, Vasil M.

    2007-04-01

    Magnetic fluids (MFs), prepared by chemical co-precipitation followed by double layer steric and electrostatic (combined) stabilization of magnetite nanoparticles dispersed in water, are presented. Several combinations of surfactants with different chain lengths (lauric acid (LA), myristic acid (MA), oleic acid (OA) and dodecyl-benzene-sulphonic acid (DBS)) were used, such as LA+LA, MA+MA, LA+DBS, MA+DBS, OA+DBS, OA+OA and DBS+DBS. Static light scattering, transmission electron microscopy, small angle neutron scattering, magnetic and magneto-rheological measurements revealed that MFs with MA+MA or LA+LA biocompatible double layer covered magnetite nanoparticles are the most stable colloidal systems among the investigated samples, and thus suitable for biomedical applications.

  20. SAXS Study of Sterically Stabilized Lipid Nanocarriers Functionalized by DNA

    NASA Astrophysics Data System (ADS)

    Angelov, Borislav; Angelova, Angelina; Filippov, Sergey; Karlsson, Göran; Terrill, Nick; Lesieur, Sylviane; Štěpánek, Petr

    2012-03-01

    The structure of novel spontaneously self-assembled plasmid DNA/lipid complexes is investigated by means of synchrotron radiation small-angle X-ray scattering (SAXS) and Cryo-TEM imaging. Liquid crystalline (LC) hydrated lipid systems are prepared using the non-ionic lipids monoolein and DOPE-PEG2000 and the cationic amphiphile CTAB. The employed plasmid DNA (pDNA) is encoding for the human protein brain-derived neurotrophic factor (BDNF). A coexistence of nanoparticulate objects with different LC inner organizations is established. A transition from bicontinuous membrane sponges, cubosome intermediates and unilamelar liposomes to multilamellar vesicles, functionalized by pDNA, is favoured upon binding and compaction of pBDNF onto the cationic PEGylated lipid nanocarriers. The obtained sterically stabilized multicompartment nanoobjects, with confined supercoiled plasmid DNA (pBDNF), are important in the context of multicompartment lipid nanocarriers of interest for gene therapy of neurodegenerative diseases.

  1. The Role of Atomic Level Steric Effects and Attractive Forces in Protein Folding

    PubMed Central

    Lammert, Heiko; Wolynes, Peter G.; Onuchic, José N.

    2011-01-01

    Protein folding into tertiary structures is controlled by an interplay of attractive contact interactions and steric effects. We investigate the balance between these contributions using structure-based models using an all-atom representation of the structure combined with a coarse-grained contact potential. Tertiary contact interactions between atoms are collected into a single broad attractive well between the Cβ atoms between each residue pair in a native contact. Through the width of these contact potentials we control their tolerance for deviations from the ideal structure and the spatial range of attractive interactions. In the compact native state dominant packing constraints limit the effects of a coarse-grained contact potential. During folding however the broad attractive potentials allow an early collapse that starts before the native local structure is completely adopted. As a consequence the folding transition is broadened and the free energy barrier is decreased. Eventually two-state folding behavior is lost completely for systems with very broad attractive potentials. The stabilization of native-like residue interactions in non-perfect geometries early in the folding process frequently leads to structural traps. Global mirror images are a notable example. These traps are penalized by the details of the repulsive interactions only after further collapse. Successful folding to the native state requires simultaneous guidance from both attractive and repulsive interactions. PMID:22081451

  2. Mid-Atlantic Wind - Overcoming the Challenges

    SciTech Connect

    Daniel F. Ancona III; Kathryn E. George; Richard P. Bowers; Dr. Lynn Sparling; Bruce Buckheit; Daniel LoBue

    2012-05-31

    This study, supported by the US Department of Energy, Wind Powering America Program, Maryland Department of Natural Resources and Chesapeake Bay Foundation, analyzed barriers to wind energy development in the Mid-Atlantic region along with options for overcoming or mitigating them. The Mid-Atlantic States including Delaware, Maryland, North Carolina and Virginia, have excellent wind energy potential and growing demand for electricity, but only two utility-scale projects have been installed to date. Reasons for this apathetic development of wind resources were analyzed and quantified for four markets. Specific applications are: 1) Appalachian mountain ridgeline sites, 2) on coastal plains and peninsulas, 3) at shallow water sites in Delaware and Chesapeake Bays, Albemarle and Pamlico Sounds, and 4) at deeper water sites off the Atlantic coast. Each market has distinctly different opportunities and barriers. The primary barriers to wind development described in this report can be grouped into four categories; state policy and regulatory issues, wind resource technical uncertainty, economic viability, and public interest in environmental issues. The properties of these typologies are not mutually independent and do interact. The report concluded that there are no insurmountable barriers to land-based wind energy projects and they could be economically viable today. Likewise potential sites in sheltered shallow waters in regional bay and sounds have been largely overlooked but could be viable currently. Offshore ocean-based applications face higher costs and technical and wind resource uncertainties. The ongoing research and development program, revision of state incentive policies, additional wind measurement efforts, transmission system expansion, environmental baseline studies and outreach to private developers and stakeholders are needed to reduce barriers to wind energy development.

  3. Mid-Atlantic Wind - Overcoming the Challenges

    SciTech Connect

    Daniel F. Ancona III; Kathryn E. George; Lynn Sparling; Bruce C. Buckheit; Daniel LoBue; and Richard P. Bowers

    2012-06-29

    This study, supported by the US Department of Energy, Wind Powering America Program, Maryland Department of Natural Resources and Chesapeake Bay Foundation, analyzed barriers to wind energy development in the Mid-Atlantic region along with options for overcoming or mitigating them. The Mid-Atlantic States including Delaware, Maryland, North Carolina and Virginia, have excellent wind energy potential and growing demand for electricity, but only two utility-scale projects have been installed to date. Reasons for this apathetic development of wind resources were analyzed and quantified for four markets. Specific applications are: 1) Appalachian mountain ridgeline sites, 2) on coastal plains and peninsulas, 3) at shallow water sites in Delaware and Chesapeake Bays, Albemarle and Pamlico Sounds, and 4) at deeper water sites off the Atlantic coast. Each market has distinctly different opportunities and barriers. The primary barriers to wind development described in this report can be grouped into four categories; state policy and regulatory issues, wind resource technical uncertainty, economic viability, and public interest in environmental issues. The properties of these typologies are not mutually independent and do interact. The report concluded that there are no insurmountable barriers to land-based wind energy projects and they could be economically viable today. Likewise potential sites in sheltered shallow waters in regional bay and sounds have been largely overlooked but could be viable currently. Offshore ocean-based applications face higher costs and technical and wind resource uncertainties. The ongoing research and development program, revision of state incentive policies, additional wind measurement efforts, transmission system expansion, environmental baseline studies and outreach to private developers and stakeholders are needed to reduce barriers to wind energy development.

  4. Overcoming Barriers: Engaging Younger Students in an Online Intercultural Exchange

    ERIC Educational Resources Information Center

    Peiser, Gillian

    2015-01-01

    This paper reports on a small-scale project involving an online school exchange between two classes of 12-/13-year olds located in the North of England and the Ruhr area of Germany. The overarching aim of the project was to develop intercultural understanding in foreign language learning through communication in an online environment. Analysing…

  5. Overcoming cellular and tissue barriers to improve liposomal drug delivery

    NASA Astrophysics Data System (ADS)

    Kohli, Aditya G.

    Forty years of liposome research have demonstrated that the anti-tumor efficacy of liposomal therapies is, in part, driven by three parameters: 1) liposome formulation and lipid biophysics, 2) accumulation and distribution in the tumor, and 3) release of the payload at the site of interest. This thesis outlines three studies that improve on each of these delivery steps. In the first study, we engineer a novel class of zwitterlipids with an inverted headgroup architecture that have remarkable biophysical properties and may be useful for drug delivery applications. After intravenous administration, liposomes accumulate in the tumor by the enhanced permeability and retention effect. However, the tumor stroma often limits liposome efficacy by preventing distribution into the tumor. In the second study, we demonstrate that depletion of hyaluronan in the tumor stroma improves the distribution and efficacy of DoxilRTM in murine 4T1 tumors. Once a liposome has distributed to the therapeutic site, it must release its payload over the correct timescale. Few facile methods exist to quantify the release of liposome therapeutics in vivo. In the third study, we outline and validate a simple, robust, and quantitative method for tracking the rate and extent of release of liposome contents in vivo. This tool should facilitate a better understanding of the pharmacodynamics of liposome-encapsulated drugs in animals. This work highlights aspects of liposome behavior that have prevented successful clinical translation and proposes alternative approaches to improve liposome drug delivery.

  6. Retaining Talent for Army 2020: Overcoming Institutional Barriers

    DTIC Science & Technology

    2012-03-19

    Assignments for Leaders, RETAL, 8. 18 Casey Wardynski, David S. Lyle, and Michael J. Colarusso , Towards a U.S. Army Officer Corps Strategy for...Opportunities (Boston: Harvard University, 2011), 17. 22 32 Wardynski, Lyle, and Colarusso , Towards a U.S. Army Officer Corps Strategy for...www.hrc.army.mil/milper/11-282 (accessed March 14, 2012). 34 Wardynski, Lyle, and Colarusso , Towards a U.S. Army Officer Corps Strategy for

  7. What Changes Education? An Action Research to Overcome Barriers

    ERIC Educational Resources Information Center

    Eskicioglu, Yeser Eroglu

    2016-01-01

    According to the National Disabled People Data Base within Ministry of Family and Social Policies (Özveri), there are 1.559.222 disabled people in Turkey. If this rate would be linked to the families of the disabled people, the number of people who spend time with disabled individuals would increase to 10 million. This number corresponds to 12.5%…

  8. Using mobile technology to overcome language barriers in medicine

    PubMed Central

    Thyer, IA; Hayne, D; Katz, DJ

    2014-01-01

    Australia has a large migrant population with variable fluency in English. Interpreting services help ensure that healthcare services are delivered appropriately to these populations. However, the use of professional interpreters in hospitals is expensive. There are also issues with service availability and convenience. Mobile devices containing software with translating abilities have promising potential to improve communication between patients and hospital staff as an adjunct to professional interpreters. It is highly convenient and inexpensive. There are concerns about the accuracy of the interpretation done with such software and more research needs to be carried out to support or allay these concerns. For now, clinically important and medicolegal related interpretation should be undertaken by professional interpreters whereas less crucial tasks may be performed with the help of interpreting software on mobile devices. PMID:25198966

  9. Bicycle helmets: overcoming barriers to use and increasing effectiveness.

    PubMed

    Rezendes, Jennifer L

    2006-02-01

    Bicycle riding is a popular recreational activity among children, yet it is not without potential severe consequences such as traumatic brain injury and death. Despite available information attesting to the benefits of the use of bicycle safety helmets, many children still do not wear them. There are several promoting and discouraging factors that influence wearing bicycle helmets. The purposes of this article are to (1) explore current research and discuss these promoting and obstructing factors to child bicycle helmet use and to (2) provide recommendations for improving the compliance of bicycle helmet use among children. Results of the literature review have significant implications for improving the safety of children.

  10. Postsecondary Correctional Education: Recognizing and Overcoming Barriers to Success

    ERIC Educational Resources Information Center

    Palmer, Shelby M.

    2012-01-01

    Postsecondary programs offering vocational training and college credit to eligible inmates have had difficulty finding a place in the U.S. correctional system. Politically motivated restrictions preventing inmates from receiving federal funds for college resulted in drastic program closures. Although new laws restored funding to select inmates,…

  11. Overcoming language barriers for non-English speaking patients.

    PubMed

    Duffy, M M; Alexander, A

    1999-10-01

    Although some of the resources or services listed may seem expensive, it is cheaper to use these than to face a malpractice suit for failure to provide patients with limited English access to services equal to those provided to English speakers. The University of California at San Francisco (UCSF), one of the top three ranking research hospitals in the U.S., had a suit filed against it by the American Civil Liberties Union (ACLU) claiming failure to provide adequate translation services for the patient population. The university is now a participant in a statewide effort to provide access to well-trained translator services to the patient population. This effort and the development of an in-house interpreter services department has contributed to a competitive edge for UCSF in the area of patient services and satisfaction as well as attracting more Medicaid patients, which increases their revenues.

  12. Using mobile technology to overcome language barriers in medicine.

    PubMed

    Chang, D T S; Thyer, I A; Hayne, D; Katz, D J

    2014-09-01

    Australia has a large migrant population with variable fluency in English. Interpreting services help ensure that healthcare services are delivered appropriately to these populations. However, the use of professional interpreters in hospitals is expensive. There are also issues with service availability and convenience. Mobile devices containing software with translating abilities have promising potential to improve communication between patients and hospital staff as an adjunct to professional interpreters. It is highly convenient and inexpensive. There are concerns about the accuracy of the interpretation done with such software and more research needs to be carried out to support or allay these concerns. For now, clinically important and medicolegal related interpretation should be undertaken by professional interpreters whereas less crucial tasks may be performed with the help of interpreting software on mobile devices.

  13. Overcoming Barriers for "Niche" Learners Through Distance Education.

    ERIC Educational Resources Information Center

    Miller, Lawrence G.; Hyatt, Sue Y.; Brennan, Joyce; Bertani, Raymond; Trevor, Thomas

    1999-01-01

    Focuses on students who fit into "niches," and discusses how the Chattanooga State Technical Community College's distance-learning program accommodates these learners. Describes five "niche" learner categories: students with disabilities, power-line maintenance technicians, emergency-service personnel, truckers, and industrial…

  14. Overcoming Barriers to Educational Restructuring: A Call for System Literacy.

    ERIC Educational Resources Information Center

    McGonagill, Grady

    The drive for systemic reform in education reflects a widespread hunger in all sectors of society to make sense of the whole, as is shown in the increasing recognition of people in organizations of the interrelatedness of the organizations' parts. However, many attempts at systemic reform are hampered by the lack of a common view of what an…

  15. Wind Power in Australia: Overcoming Technological and Institutional Barriers

    ERIC Educational Resources Information Center

    Healey, Gerard; Bunting, Andrea

    2008-01-01

    Until recently, Australia had little installed wind capacity, although there had been many investigations into its potential during the preceding decades. Formerly, state-owned monopoly utilities showed only token interest in wind power and could dictate the terms of energy debates. This situation changed in the late 1990s: Installed wind capacity…

  16. Autophagy core machinery: overcoming spatial barriers in neurons.

    PubMed

    Ariosa, Aileen R; Klionsky, Daniel J

    2016-11-01

    Autophagy is a major degradation pathway that engulfs, removes, and recycles unwanted cytoplasmic material including damaged organelles and toxic protein aggregates. One type of autophagy, macroautophagy, is a tightly regulated process facilitated by autophagy-related (Atg) proteins that must communicate effectively and act in concert to enable the de novo formation of the phagophore, its maturation into an autophagosome, and its subsequent targeting and fusion with the lysosome or the vacuole. Autophagy plays a significant role in physiology, and its dysregulation has been linked to several diseases, which include certain cancers, cardiomyopathies, and neurodegenerative diseases. Here, we summarize the key processes and the proteins that make up the macroautophagy machinery. We also briefly highlight recently uncovered molecular mechanisms specific to neurons allowing them to uniquely regulate this catabolic process to accommodate their complicated architecture and non-dividing state. Overall, these distinct mechanisms establish a conceptual framework addressing how macroautophagic dysfunction could result in maladies of the nervous system, providing possible therapeutic avenues to explore with a goal of preventing or curing such diseases.

  17. Improving The Perfect Storm: Overcoming Barriers To Climate Literacy

    NASA Astrophysics Data System (ADS)

    Tillinger, D.

    2015-12-01

    Students and scientists are trained to speak different languages. Climate science, and the geosciences more broadly, are strictly classroom topics, not subjects appropriate for casual conversation, social media, or creative projects. When students are aware of climate change through the mainstream media, it is nearly always in a political or technological context rather than a scientific one. However, given the opportunity, students are perfectly capable of not only understanding the science behind climate change, but communicating it to their peers. At the American Museum of Natural History, a group of underprivileged high school students visited Nature's Fury: The Science of Natural Disasters to learn about volcanoes, earthquakes, and climate change impacts. They were then able to write pitches and develop trailers for scientifically accurate, but still compelling, disaster movies. Arts in Parts, a creative outreach group formed as a response to Hurricane Sandy, facilitated a workshop in which younger children made mobiles from beach debris they collected while learning about the the threat of sea level rise locally and globally. Participants in an undergraduate natural disasters class wrote guides to understanding climate change that remained factual while showing great creativity and reflecting the personality of each student. Art, humor, and popular culture are the languages that society chooses to use; scientific literacy might benefit from their inclusion.

  18. Overcoming Barriers to Total Quality Management in Colleges and Universities.

    ERIC Educational Resources Information Center

    Winter, Robert S.

    1991-01-01

    To implement Total Quality Management concepts successfully, colleges and universities must change their cultures significantly. In higher education, with its organizational characteristics and traditions, authority relationships between faculty and administrators must be recognized, and some changes in the role and attention of leaders must…

  19. Overcoming Barriers to Technology Use in Teacher Preparation Programs

    ERIC Educational Resources Information Center

    Brzycki, Dolores; Dudt, Kurt

    2005-01-01

    Indiana, Clarion, and Edinboro Universities of Pennsylvania are completing a PT3 grant, funded by the U.S. Department of Education, entitled "Preparing Teachers for the Digital Age." The grant made great progress in infusing technology into the teacher preparation curriculum possible, and participating faculty know how far they have…

  20. Overcoming Barriers to Technology Adoption in Small Manufacturing Enterprises (SMEs)

    DTIC Science & Technology

    2003-06-01

    7 3.4 Adopting a Control-System-Modeling Tool.................................................8 3.5 Adapting Ecommerce and Manufacturing Execution...production of platform systems, components, and munitions is constrained not only by the surge capacity of the prime contractor, but also by the...Electronic Design Automation (EDA) tools that simplified implementing the design in hardware and software. 3.5 Adapting Ecommerce and Manufacturing

  1. Overcoming barriers to priority setting using interdisciplinary methods.

    PubMed

    Peacock, Stuart; Mitton, Craig; Bate, Angela; McCoy, Bonnie; Donaldson, Cam

    2009-10-01

    Ten years ago, Holm's highly influential paper "Goodbye to the simple solutions: the second phase of priority setting" was published [Holm S. Goodbye to the simple solutions: the second phase of priority setting in health care. British Medical Journal 1998;317:1000-7]. Whilst attending the 2nd International Conference on Priorities in Health Care in London, Holm argued that the search for a rational set of decision-making rules was no longer adequate. Instead, the priority setting process itself was now thought to be more complex. Ten years later, the Conference returns to the UK for the first time, and it is timely to describe some new tools intended to assist both researchers and decision-makers seeking to develop both rational and fair and legitimate priority setting processes. In this paper we argue that to do so, researchers and decision-makers need to adopt an interdisciplinary and collaborative approach to priority setting. We focus on program budgeting and marginal analysis (PBMA) and bring together three hitherto separate interdisciplinary strands of the PBMA literature. Our aim is to assist researchers and decision-makers seeking to effectively develop and implement PBMA in practice. Specifically, we focus on the use of multi-criteria decision analysis, participatory action research, and accountability for reasonableness, drawn from the disciplines of decision analysis, sociology, and ethics respectively.

  2. Overcoming barriers to residential conservation: do energy audits help

    SciTech Connect

    Hoffman, W.L.

    1982-12-01

    A study on the effects of energy audits on the pace and choice of household investment in energy-saving improvements in the home is reported. An evaluation based on the household's assessment of the usefulness of the audit which was provided for their home was performed. The number and types of recent conservation actions among audited and unaudited samples of households are compared. The audit's effect on household knowledge about the economically attractive options for their home and on the choice of recent improvements is assessed. Possible reasons are suggested for the weak effect of audits in stimulating activity and reorienting investment choices. (LEW)

  3. Azaphthalocyanines with fused triazolo rings: formation of sterically stressed constitutional isomers.

    PubMed

    Novakova, Veronika; Roh, Jaroslav; Gela, Petr; Kuneš, Jiří; Zimcik, Petr

    2012-05-07

    The presented work deals with synthesis and isolation of constitutional isomers of triazolo-fused azaphthalocyanines. Distribution of the isomers did not follow the statistical calculations due to steric effects of the substituents preferring the least sterically stressed C(4h) isomer.

  4. Highly durable photochromic radical complexes having no steric protections of radicals.

    PubMed

    Kobayashi, Yoichi; Mishima, Yasuhiro; Mutoh, Katsuya; Abe, Jiro

    2017-04-21

    Steric protection groups are usually necessary for stable radicals. However, here, we developed novel photochromic radical complexes which generate sterically unprotected imidazolyl and phenoxyl radicals upon UV light irradiation based on the phenoxyl-imidazolyl radical complex (PIC) framework. These photochromic compounds show excellent durability against repeated irradiation of intense nanosecond laser pulses even in polar protic solvents, such as ethanol.

  5. Modulated nematic structures induced by chirality and steric polarization

    NASA Astrophysics Data System (ADS)

    Longa, Lech; PajÄ k, Grzegorz

    2016-04-01

    What kind of one-dimensional modulated nematic structures (ODMNS) can form nonchiral and chiral bent-core and dimeric materials? Here, using the Landau-de Gennes theory of nematics, extended to account for molecular steric polarization, we study a possibility of formation of ODMNS, both in nonchiral and intrinsically chiral liquid crystalline materials. Besides nematic and cholesteric phases, we find four bulk ODMNS for nonchiral materials, two of which, to the best of our knowledge, have not been reported so far. These two structures are longitudinal (NLP) and transverse (NTP) periodic waves where the polarization field being periodic in one dimension stays parallel and perpendicular, respectively, to the wave vector. The other two phases are the twist-bend nematic phase (NTB) and the splay-bend nematic phase (NSB), but their fine structure appears more complex than that considered so far. The presence of molecular chirality converts nonchiral NTP and NSB into new NTB phases. Surprisingly, the nonchiral NLP phase can stay stable even in the presence of intrinsic chirality.

  6. Sterically allowed configuration space for amino acid dipeptides

    NASA Astrophysics Data System (ADS)

    Caballero, Diego; Maatta, Jukka; Sammalkorpi, Maria; O'Hern, Corey; Regan, Lynne

    2014-03-01

    Despite recent improvements in computational methods for protein design, we still lack a quantitative, predictive understanding of the intrinsic propensities for amino acids to be in particular backbone or side-chain conformations. This question has remained unsettled for years because of the discrepancies between different experimental approaches. To address it, I performed all-atom hard-sphere simulations of hydrophobic residues with stereo-chemical constraints and non-attractive steric interactions between non-bonded atoms for ALA, ILE, LEU and VAL dipeptide mimetics. For these hard-sphere MD simulations, I show that transitions between α-helix and β-sheet structures only occur when the bond angle τ(N -Cα - C) >110° , and the probability distribution of bond angles for structures in the `bridge' region of ϕ- ψ space is shifted to larger angles compared to that in other regions. In contrast, the relevant bond-angle distributions obtained from most molecular dynamics packages are broader and shifter to larger values. I encounter similar correlations between bond angles and side-chain dihedral angles. The success of these studies is an argument for re-incorporating local stereochemical constraints into computational protein design methodology.

  7. Characterization of sterically stabilized cisplatin liposomes by nuclear magnetic resonance.

    PubMed

    Peleg-Shulman, T; Gibson, D; Cohen, R; Abra, R; Barenholz, Y

    2001-02-09

    Extensive scientific efforts are directed towards finding new and improved platinum anticancer agents. A promising approach is the encapsulation of cisplatin in sterically stabilized, long circulating, PEGylated 100 nm liposomes. This liposomal cisplatin (STEALTH cisplatin, formerly known as SPI-77) shows excellent stability in plasma and has a longer circulation time, greater efficacy and lower toxicity than much free cisplatin. However, so far, the physicochemical characterization of STEALTH cisplatin has been limited to size distribution, drug-to-lipid ratio and stability. Information on the physical state of the drug in the liposome aqueous phases and the drug's interaction with the liposome membrane has been lacking. This study was aimed at filling this gap. We report a multinuclear NMR study in which several techniques have been used to assess the physical nature of cisplatin in liposomal formulations and if and to what extent the drug affects the liposome phospholipids. Since NMR detects only the soluble cisplatin in the liposomes and not the insoluble drug, combining NMR and atomic absorption data enables one to determine how much of the encapsulated drug is soluble in the intraliposomal aqueous phase. Our results indicate that almost all of the cisplatin remains intact during the loading process, and that the entire liposomal drug is present in a soluble form in the internal aqueous phase of the liposomes.

  8. Stereoisomers Probe Steric Zippers in Amyloid-β.

    PubMed

    Chandra, Bappaditya; Korn, Alexander; Maity, Barun Kumar; Adler, Juliane; Rawat, Anoop; Krueger, Martin; Huster, Daniel; Maiti, Sudipta

    2017-02-14

    Shape complementarity between close-packed residues plays a critical role in the amyloid aggregation process. Here, we probe such "steric zipper" interactions in amyloid-β (Aβ40), whose aggregation is linked to Alzheimer's disease, by replacing natural residues by their stereoisomers. Such mutations are expected to specifically destabilize the shape sensitive "packing" interactions, which may potentially increase their solubility and change other properties. We study the stereomutants DF19 and DL34 and also the DA2/DF4/DH6/DS8 mutant of Aβ40. F19-L34 is a critical contact in a tightly packed region of Aβ, while residues 1-9 are known to be disordered. While both DF19 and DL34 slow down the kinetics of aggregation and form amyloid fibrils efficiently, only DL34 increases the final solubility. DF19 gives rise to additional off-pathway aggregation which results in large, kinetically stable aggregates, and has lower net solubility. DA2/DF4/DH6/DS8 does not have an effect on the kinetics or the solubility. Notably, both DF19 and DL34 oligomers have a significantly lower level of interactions with lipid vesicles and live cells. We conclude that stereoisomers can cause complex site dependent changes in amyloid properties, and provide an effective tool to determine the role of individual residues in shaping the packed interiors of amyloid aggregates.

  9. Uncertainties in Steric Sea Level Change Estimation During the Satellite Altimeter Era: Concepts and Practices

    NASA Astrophysics Data System (ADS)

    MacIntosh, C. R.; Merchant, C. J.; von Schuckmann, K.

    2017-01-01

    This article presents a review of current practice in estimating steric sea level change, focussed on the treatment of uncertainty. Steric sea level change is the contribution to the change in sea level arising from the dependence of density on temperature and salinity. It is a significant component of sea level rise and a reflection of changing ocean heat content. However, tracking these steric changes still remains a significant challenge for the scientific community. We review the importance of understanding the uncertainty in estimates of steric sea level change. Relevant concepts of uncertainty are discussed and illustrated with the example of observational uncertainty propagation from a single profile of temperature and salinity measurements to steric height. We summarise and discuss the recent literature on methodologies and techniques used to estimate steric sea level in the context of the treatment of uncertainty. Our conclusions are that progress in quantifying steric sea level uncertainty will benefit from: greater clarity and transparency in published discussions of uncertainty, including exploitation of international standards for quantifying and expressing uncertainty in measurement; and the development of community "recipes" for quantifying the error covariances in observations and from sparse sampling and for estimating and propagating uncertainty across spatio-temporal scales.

  10. Uncertainties in Steric Sea Level Change Estimation During the Satellite Altimeter Era: Concepts and Practices

    NASA Astrophysics Data System (ADS)

    MacIntosh, C. R.; Merchant, C. J.; von Schuckmann, K.

    2016-10-01

    This article presents a review of current practice in estimating steric sea level change, focussed on the treatment of uncertainty. Steric sea level change is the contribution to the change in sea level arising from the dependence of density on temperature and salinity. It is a significant component of sea level rise and a reflection of changing ocean heat content. However, tracking these steric changes still remains a significant challenge for the scientific community. We review the importance of understanding the uncertainty in estimates of steric sea level change. Relevant concepts of uncertainty are discussed and illustrated with the example of observational uncertainty propagation from a single profile of temperature and salinity measurements to steric height. We summarise and discuss the recent literature on methodologies and techniques used to estimate steric sea level in the context of the treatment of uncertainty. Our conclusions are that progress in quantifying steric sea level uncertainty will benefit from: greater clarity and transparency in published discussions of uncertainty, including exploitation of international standards for quantifying and expressing uncertainty in measurement; and the development of community "recipes" for quantifying the error covariances in observations and from sparse sampling and for estimating and propagating uncertainty across spatio-temporal scales.

  11. Nano-Drugs Based on Nano Sterically Stabilized Liposomes for the Treatment of Inflammatory Neurodegenerative Diseases

    PubMed Central

    Turjeman, Keren; Bavli, Yaelle; Kizelsztein, Pablo; Schilt, Yaelle; Allon, Nahum; Katzir, Tamar Blumenfeld; Sasson, Efrat; Raviv, Uri; Ovadia, Haim; Barenholz, Yechezkel

    2015-01-01

    The present study shows the advantages of liposome-based nano-drugs as a novel strategy of delivering active pharmaceutical ingredients for treatment of neurodegenerative diseases that involve neuroinflammation. We used the most common animal model for multiple sclerosis (MS), mice experimental autoimmune encephalomyelitis (EAE). The main challenges to overcome are the drugs’ unfavorable pharmacokinetics and biodistribution, which result in inadequate therapeutic efficacy and in drug toxicity (due to high and repeated dosage). We designed two different liposomal nano-drugs, i.e., nano sterically stabilized liposomes (NSSL), remote loaded with: (a) a “water-soluble” amphipathic weak acid glucocorticosteroid prodrug, methylprednisolone hemisuccinate (MPS) or (b) the amphipathic weak base nitroxide, Tempamine (TMN). For the NSSL-MPS we also compared the effect of passive targeting alone and of active targeting based on short peptide fragments of ApoE or of β-amyloid. Our results clearly show that for NSSL-MPS, active targeting is not superior to passive targeting. For the NSSL-MPS and the NSSL-TMN it was demonstrated that these nano-drugs ameliorate the clinical signs and the pathology of EAE. We have further investigated the MPS nano-drug’s therapeutic efficacy and its mechanism of action in both the acute and the adoptive transfer EAE models, as well as optimizing the perfomance of the TMN nano-drug. The highly efficacious anti-inflammatory therapeutic feature of these two nano-drugs meets the criteria of disease-modifying drugs and supports further development and evaluation of these nano-drugs as potential therapeutic agents for diseases with an inflammatory component. PMID:26147975

  12. Comprehensive Examination of Barriers to Employment among Persons Who Are Blind or Visually Impaired.

    ERIC Educational Resources Information Center

    Crudden, Adele; McBroom, Lynn W.; Skinner, Amy L.; Moore, J. Elton

    A survey of 166 employed persons with visual impairments investigated major barriers to employment, how these barriers were overcome, and their perceptions on why they were successful in overcoming barriers when many individuals are not successful. Results of the survey indicate that the primary barriers to employment were employer attitudes,…

  13. Electronic and Steric Effects in Binding of Deep Cavitands

    PubMed Central

    Hooley, Richard J.; Shenoy, Siddhartha R.; Rebek, Julius

    2009-01-01

    A deep, self-folding cavitand responds to minor electronic differences between suitably sized adamantane guests. Binding constants range from <0.5 to 4000 M-1 for guests as similar as 1-bromoadamantane and 1-cyanoadamantane. The barriers to guest exchange also vary up to 3 kcal mol-1. PMID:18989966

  14. Use of steric encumbrance to develop conjugated nanoporous polymers for metal-free catalytic hydrogenation

    SciTech Connect

    Tian, Chengcheng; Zhu, Xiang; Abney, Carter W.; Tian, Ziqi; Jiang, De-en; Han, Kee Sung; Mahurin, Shannon M.; Washton, Nancy M.; Dai, Sheng

    2016-01-01

    The design and synthesis of metal-free heterogeneous catalysts for efficient hydrogenation remains a great challenge. Here we report a novel approach to create conjugated nanoporous polymers with efficient hydrogenation activities toward unsaturated ketones by leveraging the innate steric encumbrance. The steric bulk of the framework as well as the local sterics of the Lewis basic sites within the polymeric skeleton result in the generation of the putative catalyst. This approach opens up new possibilities for the development of innovative metal-free heterogeneous catalysts.

  15. Perspective: Vibrational-induced steric effects in bimolecular reactions

    NASA Astrophysics Data System (ADS)

    Liu, Kopin

    2015-02-01

    The concept of preferred collision geometry in a bimolecular reaction is at the heart of reaction dynamics. Exemplified by a series of crossed molecular beam studies on the reactions of a C-H stretch-excited CHD3(v1 = 1) with F, Cl, and O(3P) atoms, two types of steric control of chemical reactivity will be highlighted. A passive control is governed in a reaction with strong anisotropic entry valley that can significantly steer the incoming trajectories. This disorientation effect is illustrated by the F and O(3P) + CHD3(v1 = 1) reactions. In the former case, the long-range anisotropic interaction acts like an optical "negative" lens by deflecting the trajectories away from the favored transition-state geometry, and thus inhibiting the bond rupture of the stretch-excited CHD3. On the contrary, the interaction between O(3P) and CHD3(v1 = 1) behaves as a "positive" lens by funneling the large impact-parameter collisions into the cone of acceptance, and thereby enhances the reactivity. As for reactions with relatively weak anisotropic interactions in the entry valley, an active control can be performed by exploiting the polarization property of the infrared excitation laser to polarize the reactants in space, as demonstrated in the reaction of Cl with a pre-aligned CHD3(v1 = 1) reactant. A simpler case, the end-on versus side-on collisions, will be elucidated for demonstrating a means to disentangle the impact-parameter averaging. A few general remarks about some closely related issues, such as mode-, bond-selectivity, and Polanyi's rules, are made.

  16. Perspective: Vibrational-induced steric effects in bimolecular reactions

    SciTech Connect

    Liu, Kopin

    2015-02-28

    The concept of preferred collision geometry in a bimolecular reaction is at the heart of reaction dynamics. Exemplified by a series of crossed molecular beam studies on the reactions of a C–H stretch-excited CHD{sub 3}(v{sub 1} = 1) with F, Cl, and O({sup 3}P) atoms, two types of steric control of chemical reactivity will be highlighted. A passive control is governed in a reaction with strong anisotropic entry valley that can significantly steer the incoming trajectories. This disorientation effect is illustrated by the F and O({sup 3}P) + CHD{sub 3}(v{sub 1} = 1) reactions. In the former case, the long-range anisotropic interaction acts like an optical “negative” lens by deflecting the trajectories away from the favored transition-state geometry, and thus inhibiting the bond rupture of the stretch-excited CHD{sub 3}. On the contrary, the interaction between O({sup 3}P) and CHD{sub 3}(v{sub 1} = 1) behaves as a “positive” lens by funneling the large impact-parameter collisions into the cone of acceptance, and thereby enhances the reactivity. As for reactions with relatively weak anisotropic interactions in the entry valley, an active control can be performed by exploiting the polarization property of the infrared excitation laser to polarize the reactants in space, as demonstrated in the reaction of Cl with a pre-aligned CHD{sub 3}(v{sub 1} = 1) reactant. A simpler case, the end-on versus side-on collisions, will be elucidated for demonstrating a means to disentangle the impact-parameter averaging. A few general remarks about some closely related issues, such as mode-, bond-selectivity, and Polanyi’s rules, are made.

  17. Quantifying the role of steric constraints in nucleosome positioning.

    PubMed

    Rube, H Tomas; Song, Jun S

    2014-02-01

    Statistical positioning, the localization of nucleosomes packed against a fixed barrier, is conjectured to explain the array of well-positioned nucleosomes at the 5' end of genes, but the extent and precise implications of statistical positioning in vivo are unclear. We examine this hypothesis quantitatively and generalize the idea to include moving barriers as well as nucleosomes actively packed against a barrier. Early experiments noted a similarity between the nucleosome profile aligned and averaged across genes and that predicted by statistical positioning; however, we demonstrate that aligning random nucleosomes also generates the same profile, calling the previous interpretation into question. New rigorous results reformulate statistical positioning as predictions on the variance structure of nucleosome locations in individual genes. In particular, a quantity termed the variance gradient, describing the change in variance between adjacent nucleosomes, is tested against recent high-throughput nucleosome sequencing data. Constant variance gradients provide support for generalized statistical positioning in ∼ 50% of long genes. Genes that deviate from predictions have high nucleosome turnover and cell-to-cell gene expression variability. The observed variance gradient suggests an effective nucleosome size of 158 bp, instead of the commonly perceived 147 bp. Our analyses thus clarify the role of statistical positioning in vivo.

  18. Cyclic (Alkyl)(Amino)Carbene Complexes of Rhodium and Nickel and Their Steric and Electronic Parameters.

    PubMed

    Paul, Ursula S D; Sieck, Carolin; Haehnel, Martin; Hammond, Kai; Marder, Todd B; Radius, Udo

    2016-07-25

    N-heterocyclic carbenes (NHCs) and cyclic (alkyl)(amino)carbenes (CAACs) are of great interest, as their electronic and steric properties provide a unique class of ligands and organocatalysts. Herein, substitution reactions involving novel carbonyl complexes of rhodium and nickel were studied to provide a deeper understanding of the fundamental electronic factors characterizing CAAC(methyl) , which were compared with the large array of data available for NHC and sterically more demanding CAAC ligands.

  19. Integral steric asymmetry in the inelastic scattering of NO(X(2)Π).

    PubMed

    Brouard, M; Gordon, S D S; Hackett Boyle, A; Heid, C G; Nichols, B; Walpole, V; Aoiz, F J; Stolte, S

    2017-01-07

    The integral steric asymmetry for the inelastic scattering of NO(X) by a variety of collision partners was recorded using a crossed molecular beam apparatus. The initial state of the NO(X, v = 0, j = 1/2, Ω=1/2, ϵ=-1,f) molecule was selected using a hexapole electric field, before the NO bond axis was oriented in a static electric field, allowing probing of the scattering of the collision partner at either the N- or O-end of the molecule. Scattered NO molecules were state selectively probed using (1 + 1') resonantly enhanced multiphoton ionisation, coupled with velocity-map ion imaging. Experimental integral steric asymmetries are presented for NO(X) + Ar, for both spin-orbit manifolds, and Kr, for the spin-orbit conserving manifold. The integral steric asymmetry for spin-orbit conserving and changing transitions of the NO(X) + O2 system is also presented. Close-coupled quantum mechanical scattering calculations employing well-tested ab initio potential energy surfaces were able to reproduce the steric asymmetry observed for the NO-rare gas systems. Quantum mechanical scattering and quasi-classical trajectory calculations were further used to help interpret the integral steric asymmetry for NO + O2. Whilst the main features of the integral steric asymmetry of NO with the rare gases are also observed for the O2 collision partner, some subtle differences provide insight into the form of the underlying potentials for the more complex system.

  20. Diffusion barriers

    NASA Technical Reports Server (NTRS)

    Nicolet, M. A.

    1983-01-01

    The choice of the metallic film for the contact to a semiconductor device is discussed. One way to try to stabilize a contact is by interposing a thin film of a material that has low diffusivity for the atoms in question. This thin film application is known as a diffusion barrier. Three types of barriers can be distinguished. The stuffed barrier derives its low atomic diffusivity to impurities that concentrate along the extended defects of a polycrystalline layer. Sacrificial barriers exploit the fact that some (elemental) thin films react in a laterally uniform and reproducible fashion. Sacrificial barriers have the advantage that the point of their failure is predictable. Passive barriers are those most closely approximating an ideal barrier. The most-studied case is that of sputtered TiN films. Stuffed barriers may be viewed as passive barriers whose low diffusivity material extends along the defects of the polycrystalline host.

  1. Overcoming Stereotypes, Discovering Hidden Capitals

    ERIC Educational Resources Information Center

    Beckett, Lori; Wrigley, Terry

    2014-01-01

    This article presents a model of teacher research supported by academic partners to develop a better understanding of the barriers to education faced by young people growing up in poverty. It critiques politicians' demands for teachers to "close the gap" for ignoring the cumulative intergenerational effects of deprivation. The authors…

  2. Steric gate variants of UmuC confer UV hypersensitivity on Escherichia coli.

    PubMed

    Shurtleff, Brenna W; Ollivierre, Jaylene N; Tehrani, Mohammad; Walker, Graham C; Beuning, Penny J

    2009-08-01

    Y family DNA polymerases are specialized for replication of damaged DNA and represent a major contribution to cellular resistance to DNA lesions. Although the Y family polymerase active sites have fewer contacts with their DNA substrates than replicative DNA polymerases, Y family polymerases appear to exhibit specificity for certain lesions. Thus, mutation of the steric gate residue of Escherichia coli DinB resulted in the specific loss of lesion bypass activity. We constructed variants of E. coli UmuC with mutations of the steric gate residue Y11 and of residue F10 and determined that strains harboring these variants are hypersensitive to UV light. Moreover, these UmuC variants are dominant negative with respect to sensitivity to UV light. The UV hypersensitivity and the dominant negative phenotype are partially suppressed by additional mutations in the known motifs in UmuC responsible for binding to the beta processivity clamp, suggesting that the UmuC steric gate variant exerts its effects via access to the replication fork. Strains expressing the UmuC Y11A variant also exhibit decreased UV mutagenesis. Strikingly, disruption of the dnaQ gene encoding the replicative DNA polymerase proofreading subunit suppressed the dominant negative phenotype of a UmuC steric gate variant. This could be due to a recruitment function of the proofreading subunit or involvement of the proofreading subunit in a futile cycle of base insertion/excision with the UmuC steric gate variant.

  3. Epistemological barriers to radical behaviorism.

    PubMed

    O'Donohue, W T; Callaghan, G M; Ruckstuhl, L E

    1998-01-01

    The historian and philosopher of science Gaston Bachelard proposed the concept of epistemological barriers to describe the intellectual challenges encountered by scientists in their work. In order to embrace novel ways of approaching a problem in science, scientists must overcome barriers or obstacles posed by their prior views. For example, Einsteinian physics presents scientists with claims that space is curved and that time and space are on the same continuum. We utilize Bachelard's concept of epistemological barriers to describe the differences between the intellectual journeys students pursuing advanced studies face when attempting to accept cognitive psychology or radical behaviorism. We contend that the folk psychological beliefs that students typically hold when entering these studies pose less challenge to cognitive psychology than to radical behaviorism. We also suggest that these barriers may also partly be involved in the problematic exegesis that has plagued radical behaviorism. In close, we offer some suggestions for dealing with these epistemological barriers.

  4. Epistemological barriers to radical behaviorism

    PubMed Central

    O'Donohue, William T.; Callaghan, Glenn M.; Ruckstuhl, L. E.

    1998-01-01

    The historian and philosopher of science Gaston Bachelard proposed the concept of epistemological barriers to describe the intellectual challenges encountered by scientists in their work. In order to embrace novel ways of approaching a problem in science, scientists must overcome barriers or obstacles posed by their prior views. For example, Einsteinian physics presents scientists with claims that space is curved and that time and space are on the same continuum. We utilize Bachelard's concept of epistemological barriers to describe the differences between the intellectual journeys students pursuing advanced studies face when attempting to accept cognitive psychology or radical behaviorism. We contend that the folk psychological beliefs that students typically hold when entering these studies pose less challenge to cognitive psychology than to radical behaviorism. We also suggest that these barriers may also partly be involved in the problematic exegesis that has plagued radical behaviorism. In close, we offer some suggestions for dealing with these epistemological barriers. PMID:22478314

  5. Carbamate stabilities of sterically hindered amines from quantum chemical methods: relevance for CO2 capture.

    PubMed

    Gangarapu, Satesh; Marcelis, Antonius T M; Zuilhof, Han

    2013-12-02

    The influence of electronic and steric effects on the stabilities of carbamates formed from the reaction of CO2 with a wide range of alkanolamines was investigated by quantum chemical methods. For the calculations, B3LYP, M11-L, MP2, and spin-component-scaled MP2 (SCS-MP2) methods were used, coupled with SMD and SM8 solvation models. A reduction in carbamate stability leads to an increased CO2 absorption capacity of the amine and a reduction of the energy required for solvent regeneration. Important factors for the reduction of the carbamate stability were an increase in steric hindrance around the nitrogen atom, charge on the N atom and intramolecular hydrogen bond strength. The present study indicates that secondary ethanolamines with sterically hindering groups near the N atom show significant potential as candidates for industrial CO2-capture solvents.

  6. Overcoming "the Valley of Death".

    PubMed

    McIntyre, Robin A

    2014-01-01

    On a global level there are major challenges arising from climate change, resource use and changing age demographics. These issues have created a global marketplace for novel innovative products and solutions which can help to combat and overcome these challenges which have created significant commercial opportunities for companies, particularly for small and medium size enterprises or SMEs. Companies most likely to take advantage of these opportunities will be those which can innovate in a timely manner. Innovation significantly contributes to higher productivity and economic growth, and is core to a company's competitiveness within often challenging marketplaces. However, many factors can stifle innovation. Companies can struggle to identify finance for early-stage development, the returns can be difficult to predict, and the innovation 'landscape' is often complex and unclear. This brief review describes some of the main issues with commercialising innovative ideas and provides guidance with respect to the often complicated funding landscape both on a National and European level.

  7. Barriers to Asthma Management as Identified by School Nurses

    ERIC Educational Resources Information Center

    Quaranta, Judith E.; Spencer, Gale A.

    2016-01-01

    Asthma rates are increasing in children. School nurses have opportunities to care for children with asthma but need to overcome barriers impacting their ability to manage asthma in the school setting. This study (a) assessed barriers present in the school setting, (b) determined the impact of barriers on performance of asthma management behaviors,…

  8. Vehicle barrier

    DOEpatents

    Hirsh, Robert A.

    1991-01-01

    A vehicle security barrier which can be conveniently placed across a gate opening as well as readily removed from the gate opening to allow for easy passage. The security barrier includes a barrier gate in the form of a cable/gate member in combination with laterally attached pipe sections fixed by way of the cable to the gate member and lateral, security fixed vertical pipe posts. The security barrier of the present invention provides for the use of cable restraints across gate openings to provide necessary security while at the same time allowing for quick opening and closing of the gate areas without compromising security.

  9. New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and poly(ethylene glycol)-cholesterol conjugates.

    PubMed Central

    Beugin, S; Edwards, K; Karlsson, G; Ollivon, M; Lesieur, S

    1998-01-01

    Monomethoxypoly(ethylene glycol) cholesteryl carbonates (M-PEG-Chol) with polymer chain molecular weights of 1000 (M-PEG1000-Chol) and 2000 (M-PEG2000-Chol) have been newly synthesized and characterized. Their aggregation behavior in mixture with diglycerol hexadecyl ether (C16G2) and cholesterol has been examined by cryotransmission electron microscopy, high-performance gel exclusion chromatography, and quasielastic light scattering. Nonaggregated, stable, unilamellar vesicles were obtained at low polymer levels with optimal shape and size homogeneity at cholesteryl conjugate/ lipids ratios of 10 mol% M-PEG1000-Chol or 5 mol% M-PEG2000-Chol, corresponding to the theoretically predicted brush conformational state of the PEG chains. At 20 mol% M-PEG1000-Chol or 10 mol% M-PEG2000-Chol, the saturation threshold of the C16G2/cholesterol membrane in polymer is exceeded, and open disk-shaped aggregates are seen in coexistence with closed vesicles. Higher levels up to 30 mol% lead to the complete solubilization of the vesicles into disk-like structures of decreasing size with increasing PEG content. This study underlines the bivalent role of M-PEG-Chol derivatives: while behaving as solubilizing surfactants, they provide an efficient steric barrier, preventing the vesicles from aggregation and fusion over a period of at least 2 weeks. PMID:9635773

  10. Implications of sterically constrained n-butane oxidation reactions on the reaction mechanism and selectivity to 1-butanol

    NASA Astrophysics Data System (ADS)

    Dix, Sean T.; Gómez-Gualdrón, Diego A.; Getman, Rachel B.

    2016-11-01

    Density functional theory (DFT) is used to analyze the reaction network in n-butane oxidation to 1-butanol over a Ag/Pd alloy catalyst under steric constraints, and the implications on the ability to produce 1-butanol selectively using MOF-encapsulated catalysts are discussed. MOFs are porous crystalline solids comprised of metal nodes linked by organic molecules. Recently, they have been successfully grown around metal nanoparticle catalysts. The resulting porous networks have been shown to promote regioselective chemistry, i.e., hydrogenation of trans-1,3-hexadiene to 3-hexene, presumably by forcing the linear alkene to stand "upright" on the catalyst surface and allowing only the terminal C-H bonds to be activated. In this work, we extend this concept to alkane oxidation. Our goal is to determine if a MOF-encapsulated catalyst could be used to selectively produce 1-butanol. Reaction energies and activation barriers are presented for more than 40 reactions in the pathway for n-butane oxidation. We find that C-H bond activation proceeds through an oxygen-assisted pathway and that butanal and 1-butanol are some of the possible products.

  11. Importance of steric effects on the efficiency and fidelity of transcription by T7 RNA polymerase.

    PubMed

    Ulrich, Sébastien; Kool, Eric T

    2011-11-29

    DNA-dependent RNA polymerases such as T7 RNA polymerase (T7 RNAP) perform the transcription of DNA into mRNA with high efficiency and high fidelity. Although structural studies have provided a detailed account of the molecular basis of transcription, the relative importance of factors like hydrogen bonds and steric effects remains poorly understood. We report herein the first study aimed at systematically probing the importance of steric and electrostatic effects on the efficiency and fidelity of DNA transcription by T7 RNAP. We used synthetic nonpolar analogues of thymine with sizes varying in subangstrom increments to probe the steric requirements of T7 RNAP during the elongation mode of transcription. Enzymatic assays with internal radiolabeling were performed to compare the efficiency of transcription of modified DNA templates with a natural template containing thymine as a reference. Furthermore, we analyzed effects on the fidelity by measuring the composition of RNA transcripts by enzymatic digestion followed by two-dimensional thin layer chromatography separation. Our results demonstrate that hydrogen bonds play an important role in the efficiency of transcription but, interestingly, do not appear to be required for faithful transcription. Steric effects (size and shape variations) are found to be significant both in insertion of a new RNA base and in extension beyond it.

  12. Steric and energetic properties of the Cl- C6H6 Arn heterocluster

    NASA Astrophysics Data System (ADS)

    Albertí, M.; Castro, A.; Laganà, A.; Moix, M.; Pirani, F.; Cappelletti, D.

    2006-04-01

    The dynamics of heteroclusters containing argon, benzene and chlorine has been investigated using a recently proposed potential energy functional that takes into account both the electrostatic and the non-electrostatic contributions to the overall noncovalent interaction. Related steric and energetic properties are compared with those homologous cationic clusters.

  13. Micro-flow synthesis and structural analysis of sterically crowded diimine ligands with five aryl rings

    PubMed Central

    Tanabe, Nobutake; Tannna, Akio; Konishi, Yohei; Takahashi, Takashi

    2013-01-01

    Summary Sterically crowded diimine ligands with five aryl rings were prepared in one step in good yields using a micro-flow technique. X-ray crystallographic analysis revealed the detailed structure of the bulky ligands. The nickel complexes prepared from the ligands exerted high polymerization activity in the ethylene homopolymerization and copolymerization of ethylene with polar monomers. PMID:24367397

  14. Effect of sterically demanding substituents on the conformational stability of the collagen triple helix.

    PubMed

    Erdmann, Roman S; Wennemers, Helma

    2012-10-17

    The effect of sterically demanding groups at proline residues on the conformational stability of the collagen triple helix was examined. The thermal stabilities (T(m) and ΔG) of eight different triple helices derived from collagen model peptides with (4R)- or (4S)-configured amidoprolines bearing either methyl or bulkier tert-butyl groups in the Xaa or Yaa position were determined and served as a relative measure for the conformational stability of the corresponding collagen triple helices. The results show that sterically demanding substituents are tolerated in the collagen triple helix when they are attached to (4R)-configured amidoprolines in the Xaa position or to (4S)-configured amidoprolines in the Yaa position. Structural studies in which the preferred conformation of (4R)- or (4S)-configured amidoproline were overlaid with the Pro and Hyp residues within a crystal structure of collagen revealed that the sterically demanding groups point to the outside of these two triple helices and thereby do not interfere with the formation of the triple helix. In all of the other examined collagen derivatives with lower stability of the triple helices, the acetyl or pivaloyl residues point toward the inside of the triple helix and clash with a residue of the neighboring strand. The results also revealed that unfavorable steric dispositions affect the conformational stability of the collagen triple helix more than unfavorable ring puckers of the proline residues. The results are useful for the design of functionalized collagen based materials.

  15. OXIDATION OF CYCLOHEXANE WITH AIR CATALYZED BY A STERICALLY HINDERED IRON (II) COMPLEX

    EPA Science Inventory

    Oxidation of Cyclohexane with Air Catalyzed by a Sterically Hindered Iron(II) Complex.


    Thomas M. Becker, Michael A. Gonzalez*

    United States Environmental Protection Agency; National Risk Management Research Laboratory; Sustainable Technology Division; Clean Pr...

  16. Steric and mass-induced sea level variations in the Mediterranean Sea revisited

    NASA Astrophysics Data System (ADS)

    GarcíA-GarcíA, D.; Chao, B. F.; Boy, J.-P.

    2010-12-01

    The total sea level variation (SLV) is the combination of steric and mass-induced SLV, whose exact shares are key to understanding the oceanic response to climate system changes. Total SLV can be observed by radar altimetry satellites such as TOPEX/POSEIDON and Jason 1/2. The steric SLV can be computed through temperature and salinity profiles from in situ measurements or from ocean general circulation models (OGCM), which can assimilate the said observations. The mass-induced SLV can be estimated from its time-variable gravity (TVG) signals. We revisit this problem in the Mediterranean Sea estimating the observed, steric, and mass-induced SLV, for the latter we analyze the latest TVG data set from the GRACE (Gravity Recovery and Climate Experiment) satellite mission launched in 2002, which is 3.5 times longer than in previous studies, with the application of a two-stage anisotropic filter to reduce the noise in high-degree and -order spherical harmonic coefficients. We confirm that the intra-annual total SLV are only produced by water mass changes, a fact explained in the literature as a result of the wind field around the Gibraltar Strait. The steric SLV estimated from the residual of "altimetry minus GRACE" agrees in phase with that estimated from OGCMs and in situ measurements, although showing a higher amplitude. The net water fluxes through both the straits of Gibraltar and Sicily have also been estimated accordingly.

  17. Steric stabilization of nonaqueous silicon slips. I - Control of particle agglomeration and packing. II - Pressure casting of powder compacts

    NASA Technical Reports Server (NTRS)

    Kerkar, Awdhoot V.; Henderson, Robert J. M.; Feke, Donald L.

    1990-01-01

    The application of steric stabilization to control particle agglomeration and packing of silicon powder in benzene and trichloroethylene is reported. The results provide useful guidelines for controlling unfavorable particle-particle interactions during nonaqueous processing of silicon-based ceramic materials. The application of steric stabilization to the control and improvement of green processing of nonaqueous silicon slips in pressure consolidation is also demonstrated.

  18. Bioenergetic Progress and Heat Barriers

    NASA Astrophysics Data System (ADS)

    Zotin, A. A.; Lamprecht, I.; Zotin, A. I.

    2001-07-01

    Progressing biological evolution is discussed in the framework of nonequilibrium thermodynamics. It is connected with an increase of the mass specific standard metabolism given by coefficient a in the allometric relation (1) between oxygen consumption rate and body mass of an animal. Three “heat barriers” are found in the course of such a bioenergetic evolution. The first heat barrier concerns an animal's overheating during active movement and is overcome by the development of thermoregulation and the appearance of homeothermic animals. A second barrier arises when the coefficient a reaches values connected with lethal body temperatures. The transition across this second heat barrier occurs as result of reasonable activities and the appearance of civilization. The third heat barrier will arise during the further development of human civilization, connected with a highly increased energy production and a fatal warming of the Earth atmosphere. The manner to overcome this barrier will probably depend on the assimilation of space and the establishment of energy consuming industries outside the Earth. The bioenergetic evolution discussed in this paper does not exclude other trends of evolution, e.g. increase of size, and does not mean to be the only aspect of biological evolution.

  19. Barriers to cancer screening.

    PubMed

    Womeodu, R J; Bailey, J E

    1996-01-01

    Many barriers to cancer screening have been summarized and discussed. Barriers have been documented in all patient populations, but some groups such as ethnic minorities and the elderly face unique barriers. The barriers to cancer screening, are multifactorial, but much of the responsibility for change must lie with health care providers and the health care delivery industry. This is not to free the patient of all responsibility, but some significant barriers are beyond their direct control. Take, for example, socioeconomic status, disease knowledge, and culturally related perceptions and myths about cancer detection and treatment. The health care industry must do a better job identifying and overcoming these barriers. The significant effects of provider counseling and advice must not be underestimated. Patients must first be advised, and then further actions must be taken if they reject the screening advice. Did they refuse adherence to recommendations because they do not view themselves as susceptible, because of overwhelming personal barriers, or because of a fatalistic attitude toward cancer detection and treatment? If that is the case, physicians and health care institutions must attempt to change perceptions, educate, and personalize the message so that patients accept their disease susceptibility [table: see text]. Multiple patient and provider risk factors have been identified that can be used to target patients particularly at high risk for inadequate cancer screening and providers at high risk for performing inadequate screening. Research has clearly demonstrated the effectiveness of interventions to improve tracking of patient and physician compliance with screening recommendations. Further research is needed to show the impact of managed-care penetration and payer status on screening efforts, and incentive schemes need to be tested that reward institutions and third-party payers who develop uniform standards and procedures for cancer screening. The

  20. Influence of ion sterics on diffusiophoresis and electrophoresis in concentrated electrolytes

    NASA Astrophysics Data System (ADS)

    Stout, Robert F.; Khair, Aditya S.

    2017-01-01

    We quantify the diffusiophoresis and electrophoresis of a uniformly charged, spherical colloid in a binary electrolyte using modified Poisson-Nernst-Planck equations that account for steric repulsion between finite sized ions. Specifically, we utilize the Bikerman (Bik) lattice gas model and the Carnahan-Starling (CS) and Boublik-Mansoori-Carnahan-Starling-Leland (BMCSL) equations of state for monodisperse and polydisperse, respectively, hard spheres. We compute the phoretic mobility for weak applied fields using an asymptotic approach for thin diffuse layers, where ion steric effects are expected to be most prevalent. The thin diffuse layer limit requires λD/R →0 , where λD is the Debye screening length and R is the particle radius; this limit is readily attained for micron-sized colloids in concentrated electrolytic solutions. It is well known that the classic Poisson-Boltzmann (PB) model for pointlike, noninteracting ions leads to a prediction of a maximum in both the diffusiophoretic and electrophoretic mobilities with increasing particle zeta potential (at fixed λD/R ). In contrast, we find that ion sterics essentially eliminate this maximum (for reasonably attainable zeta potentials) and increase the mobility relative to PB. Next, we consider the more experimentally relevant case of a particle with a constant surface charge density and vary the electrolyte concentration, neglecting charge regulation on surface active sites. Rather surprisingly, there is little difference between the predictions of the four models (PB, Bik, CS, and BMCSL) for electrophoretic mobility in concentrated solutions, at reasonable surface charge densities (˜1 -10 μ C /cm2 ). This is because as the concentration increases, the zeta potential is reduced (to below the thermal voltage for concentrations above about 1 M) and therefore the diffuse layer structure is largely unaffected by ion sterics. For gradients of symmetric electrolytes (equal diffusivities, charge, and size

  1. Using steric hindrance to design new inhibitors of class C beta-lactamases

    SciTech Connect

    Trehan, Indi; Morandi, F.; Blaszczak, L.C.; Shoichet, Brian K.

    2010-03-08

    {beta}-lactamases confer resistance to {beta}-lactam antibiotics such as penicillins and cephalosporins. However, {beta}-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of {beta}-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R1 side chain of {beta}-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective {beta}-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of the penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design.

  2. Tuning steric and electronic effects in transition-metal β-diketiminate complexes

    PubMed Central

    Chen, Chi; Bellows, Sarina M.; Holland, Patrick L.

    2015-01-01

    β-Diketiminates are widely used supporting ligands for building a range of metal complexes with different oxidation states, structures, and reactivities. This Perspective summarizes the steric and electronic influences of ligand substituents on these complexes, with an eye toward informing the design of new complexes with optimized properties. The backbone and N-aryl substituents can give significant steric effects on structure, reactivity and selectivity of reactions. The electron density on the metal can be tuned by installation of electron withdrawing or donating groups on the β-diketiminate ligand as well. Examples are shown from throughout the transition metal series to demonstrate different types of effects attributable to systematic variation of β-diketiminate ligands. PMID:26244489

  3. Steric vs electronic effects in binary uranyl alkoxides: A spectroscopic perspective

    NASA Astrophysics Data System (ADS)

    Morris, David E.; Wilkerson, Marianne P.; Burns, Carol J.; Scott, Brian L.; Wilkerson, Marianne P.; Paine, Robert T.

    2000-07-01

    Recent advances in the non-aqueous alkoxide chemistry of UO22+ have provided the wherewithal to prepare and isolate a broad range of discrete molecular uranyl entities both as solids and in aprotic solvents in which it is possible to tune the ligand basicity and steric encumbrance. Uranyl complexes have been isolated as monomers, dimers, and higher order oligomers. These complexes afford an opportunity to examine in some detail the relative importance of ligand basicity and steric demand in directing structural preferences (monomer vs. dimer, cis vs. trans isomers) and in determining electronic structural properties and relative bond strengths in the "yl" and equatorial bonds. In the present report the electronic and vibrational spectroscopic data for a series of uranyl alkoxides are correlated with molecular structural data to examine trends in electronic structure and bonding and compare these results with existing models based on the more classical uranyl coordination compounds.

  4. Steric effect in the energy transfer reaction of Ar(3P2)+N2

    NASA Astrophysics Data System (ADS)

    Watanabe, D.; Ohoyama, H.; Matsumura, T.; Kasai, T.

    2006-08-01

    Steric effect for N2(C,Πu3) formation in the energy transfer reaction of Ar(P23)+N2 was directly measured by using an oriented Ar(P23,MJ=2) beam at a collision energy of 0.06eV. The N2(C,Πu3) chemiluminescence intensity was measured as a function of the magnetic orientation field direction in the collision frame. A significant alignment effect on the energy transfer probability was observed. The relative reactivity for each magnetic substate in the collision frame σ∣MJ'∣ was determined to be σ∣2∣:σ∣1∣:σ0=0.50:0.60:1.00. It is suggested that the observed steric effect is primarily due to the favorable configuration of the 3p orbital for the efficient overlap with the 2σu molecular orbital of N2.

  5. Electrocatalytic Alcohol Oxidation with TEMPO and Bicyclic Nitroxyl Derivatives: Driving Force Trumps Steric Effects.

    PubMed

    Rafiee, Mohammad; Miles, Kelsey C; Stahl, Shannon S

    2015-11-25

    Bicyclic nitroxyl derivatives, such as 2-azaadamantane N-oxyl (AZADO) and 9-azabicyclo[3.3.1]nonane N-oxyl (ABNO), have emerged as highly effective alternatives to TEMPO-based catalysts for selective oxidation reactions (TEMPO = 2,2,6,6-tetramethyl-1-piperidine N-oxyl). Their efficacy is widely attributed to their smaller steric profile; however, electrocatalysis studies described herein show that the catalytic activity of nitroxyls is more strongly affected by the nitroxyl/oxoammonium redox potential than by steric effects. The inexpensive, high-potential TEMPO derivative, 4-acetamido-TEMPO (ACT), exhibits higher electrocatalytic activity than AZADO and ABNO for the oxidation of primary and secondary alcohols. Mechanistic studies provide insights into the origin of these unexpected reactivity trends. The superior activity of ACT is especially noteworthy at high pH, where bicyclic nitroxyls are inhibited by formation of an oxoammonium hydroxide adduct.

  6. Chromatography Models with Langmuir and Steric Mass Action Adsorption Isotherms are of Differential Index One

    NASA Astrophysics Data System (ADS)

    von Lieres, Eric

    2010-09-01

    Chromatography is commonly applied for the separation of bio-molecules in pharmaceutical industry, and chromatography models are increasingly applied for rational process analysis and optimization. A rapid equilibrium assumption is often applied for the adsorption equation, which results in a non-linear system of partial differential-algebraic equations (PDAEs). In this contribution a proof is given, that these PDAEs are of differential index one for the two most prominent isotherm models, Langmuir and steric mass action (SMA).

  7. Regulation of Dscam exon 17 alternative splicing by steric hindrance in combination with RNA secondary structures.

    PubMed

    Yue, Yuan; Li, Guoli; Yang, Yun; Zhang, Wenjing; Pan, Huawei; Chen, Ran; Shi, Feng; Jin, Yongfeng

    2013-12-01

    The gene Down syndrome cell adhesion molecule (Dscam) potentially encodes 38 016 distinct isoforms in Drosophila melanogaster via mutually exclusive splicing. Here we reveal a combinatorial mechanism of regulation of Dscam exon 17 mutually exclusive splicing through steric hindrance in combination with RNA secondary structure. This mutually exclusive behavior is enforced by steric hindrance, due to the close proximity of the exon 17.2 branch point to exon 17.1 in Diptera, and the interval size constraint in non-Dipteran species. Moreover, intron-exon RNA structures are evolutionarily conserved in 36 non-Drosophila species of six distantly related orders (Diptera, Lepidoptera, Coleoptera, Hymenoptera, Hemiptera, and Phthiraptera), which regulates the selection of exon 17 variants via masking the splice site. By contrast, a previously uncharacterized RNA structure specifically activated exon 17.1 by bringing splice sites closer together in Drosophila, while the other moderately suppressed exon 17.1 selection by hindering the accessibility of polypyrimidine sequences. Taken together, these data suggest a phylogeny of increased complexity in regulating alternative splicing of Dscam exon 17 spanning more than 300 million years of insect evolution. These results also provide models of the regulation of alternative splicing through steric hindrance in combination with dynamic structural codes.

  8. Steric and Mass-Induced Sea Level Variations in the Mediterranean Sea, Revisited

    NASA Astrophysics Data System (ADS)

    Garcia-Garcia, D.; Chao, B. F.; Boy, J.-P.

    2009-04-01

    Observed by radar altimetry satellites such as TOPEX/Poseidon (T/P) and Jason-1/2, the total Sea Level Variations (SLV) are produced by a combination of the steric and mass-induced components. The steric SLV can be computed from in situ measurements of temperature and salinity profiles, or from Ocean General Circulation Models (OGCM) that can assimilate those measurements. Mass-induced SLV can be estimated, since 2002, from Time-Variable Gravity (TVG) measurements by the GRACE satellite mission. This methodology has been successfully applied in estimation of the global ocean mass-induced SLV. However, some difficulties arise when studying semi-enclosed basins due to land aliasing of the GRACE TVG signal. The problem is specially complicated in the Mediterranean Sea as reported in previous studies. We revisit this problem analyzing release 4 of the GRACE data set, which represents a time series 3 times longer than in previous studies, by means of new and more efficient filters to reduce the noise in the high degree and order spherical harmonics coefficients. The seasonal and non-seasonal signals are analyzed. From the comparison of GRACE with altimetry data a general underestimation of the steric term is observed in the OGCMs used.

  9. Math Is Like a Scary Movie? Helping Young People Overcome Math Anxiety

    ERIC Educational Resources Information Center

    Kulkin, Margaret

    2016-01-01

    Afterschool teachers who tutor students or provide homework help have a unique opportunity to help students overcome the social or emotional barriers that so often block learning. They can embrace a creative and investigative approach to math learning. Margaret Kulkin's interest in being a math attitude "myth-buster" led her to apply to…

  10. Glucocorticosteroids in nano-sterically stabilized liposomes are efficacious for elimination of the acute symptoms of experimental cerebral malaria.

    PubMed

    Waknine-Grinberg, Judith H; Even-Chen, Simcha; Avichzer, Jasmine; Turjeman, Keren; Bentura-Marciano, Annael; Haynes, Richard K; Weiss, Lola; Allon, Nahum; Ovadia, Haim; Golenser, Jacob; Barenholz, Yechezkel

    2013-01-01

    Cerebral malaria is the most severe complication of Plasmodium falciparum infection, and a leading cause of death in children under the age of five in malaria-endemic areas. We report high therapeutic efficacy of a novel formulation of liposome-encapsulated water-soluble glucocorticoid prodrugs, and in particular β-methasone hemisuccinate (BMS), for treatment of experimental cerebral malaria (ECM), using the murine P. berghei ANKA model. BMS is a novel derivative of the potent steroid β-methasone, and was specially synthesized to enable remote loading into nano-sterically stabilized liposomes (nSSL), to form nSSL-BMS. The novel nano-drug, composed of nSSL remote loaded with BMS, dramatically improves drug efficacy and abolishes the high toxicity seen upon administration of free BMS. nSSL-BMS reduces ECM rates in a dose-dependent manner and creates a survival time-window, enabling administration of an antiplasmodial drug, such as artemisone. Administration of artemisone after treatment with the nSSL-BMS results in complete cure. Treatment with BMS leads to lower levels of cerebral inflammation, demonstrated by changes in cytokines, chemokines, and cell markers, as well as diminished hemorrhage and edema, correlating with reduced clinical score. Administration of the liposomal formulation results in accumulation of BMS in the brains of sick mice but not of healthy mice. This steroidal nano-drug effectively eliminates the adverse effects of the cerebral syndrome even when the treatment is started at late stages of disease, in which disruption of the blood-brain barrier has occurred and mice show clear signs of neurological impairment. Overall, sequential treatment with nSSL-BMS and artemisone may be an efficacious and well-tolerated therapy for prevention of CM, elimination of parasites, and prevention of long-term cognitive damage.

  11. Synthesis of sterically hindered ortho-substituted tetraphenylethenes. Electronic effects in the McMurry olefination reaction.

    PubMed

    Chung, Mee-Kyung; Qi, Guizhong; Stryker, Jeffrey M

    2006-03-30

    [reaction: see text] Contrary to literature consensus, the McMurry olefination reaction can be extended to the direct synthesis of sterically encumbered tetrakis(2-substituted) tetraphenylethenes from the corresponding 2,2'-disubstituted benzophenones. The reaction exploits previously unrecognized substrate-based electronic effects that dominate over otherwise controlling steric considerations and provides highly efficient access to derivatives of tetrakis(2-hydroxyphenyl)ethene, a novel preorganized ligand system for polymetallic coordination chemistry and catalysis.

  12. Language barriers

    PubMed Central

    Ngwakongnwi, Emmanuel; Hemmelgarn, Brenda R.; Musto, Richard; King-Shier, Kathryn M.; Quan, Hude

    2012-01-01

    Abstract Objective To assess use of regular medical doctors (RMDs), as well as awareness and use of telephone health lines or telehealth services, by official language minorities (OLMs) in Canada. Design Analysis of data from the 2006 postcensal survey on the vitality of OLMs. Setting Canada. Participants In total, 7691 English speakers in Quebec and 12 376 French speakers outside Quebec, grouped into those who experienced language barriers and those with no language barriers. Main outcome measures Health services utilization (HSU) by the presence of language barriers; HSU measures included having an RMD, use of an RMD’s services, and awareness of and use of telephone health lines or telehealth services. Multivariable models examined the associations between HSU and language barriers. Results After adjusting for age and sex, English speakers residing in Quebec with limited proficiency in French were less likely to have RMDs (adjusted odds ratio [AOR] 0.66, 95% CI 0.50 to 0.87) and to use the services of their RMDs (AOR 0.65, 95% CI 0.50 to 0.86), but were more likely to be aware of the existence of (AOR 1.50, 95% CI 1.16 to 1.93) and to use (AOR 1.43, 95% CI 0.97 to 2.11) telephone health lines or telehealth services. This pattern of having and using RMDs and telehealth services was not observed for French speakers residing outside of Quebec. Conclusion Overall we found variation in HSU among the language barrier populations, with lower use observed in Quebec. Age older than 45 years, male sex, being married or in common-law relationships, and higher income were associated with having RMDs for OLMs. PMID:23242902

  13. Steric effects in the dynamics of electrolytes at large applied voltages. I. Double-layer charging

    NASA Astrophysics Data System (ADS)

    Kilic, Mustafa Sabri; Bazant, Martin Z.; Ajdari, Armand

    2007-02-01

    The classical Poisson-Boltzmann (PB) theory of electrolytes assumes a dilute solution of point charges with mean-field electrostatic forces. Even for very dilute solutions, however, it predicts absurdly large ion concentrations (exceeding close packing) for surface potentials of only a few tenths of a volt, which are often exceeded, e.g., in microfluidic pumps and electrochemical sensors. Since the 1950s, several modifications of the PB equation have been proposed to account for the finite size of ions in equilibrium, but in this two-part series, we consider steric effects on diffuse charge dynamics (in the absence of electro-osmotic flow). In this first part, we review the literature and analyze two simple models for the charging of a thin double layer, which must form a condensed layer of close-packed ions near the surface at high voltage. A surprising prediction is that the differential capacitance typically varies nonmonotonically with the applied voltage, and thus so does the response time of an electrolytic system. In PB theory, the differential capacitance blows up exponentially with voltage, but steric effects actually cause it to decrease while remaining positive above a threshold voltage where ions become crowded near the surface. Other nonlinear effects in PB theory are also strongly suppressed by steric effects: The net salt adsorption by the double layers in response to the applied voltage is greatly reduced, and so is the tangential “surface conduction” in the diffuse layer, to the point that it can often be neglected compared to bulk conduction (small Dukhin number).

  14. Steric stabilization of Pickering emulsions for the efficient synthesis of polymeric microcapsules.

    PubMed

    Salari, Joris W O; van Heck, Jeroen; Klumperman, Bert

    2010-09-21

    It is commonly known that Pickering emulsions are extremely stable against coalescence and are, therefore, potentially interesting for the synthesis of new materials, such as colloidosomes, microcapsules, composite particles, foams, and so on. However, for the efficient synthesis of such materials, one also has to consider the colloidal stability against aggregation, which is often neglected. In this study, it is demonstrated that steric stabilization is provided to Pickering emulsion droplets by the adsorption of poly(styrene-block-ethylene-co-propylene) (pS-b-EP) and that it is a requirement for the efficient synthesis of polymeric microcapsules. Monodisperse polystyrene particles of 648 nm are synthesized by soap-free emulsion polymerization. A model Pickering emulsion is then formed by the addition of sodium chloride at a critical concentration of 325 mM and mixing it with either heptane or decane. Subsequently, pS-b-EP is added to the Pickering emulsion to provide steric stabilization. Size exclusion chromatography is used to prove and quantify the adsorption of pS-b-EP onto the Pickering emulsion droplets. A maximum surface coverage of 1.3 mg/m(2) is obtained after 2 h, which is approximately one-third of the adsorption on a pure pS surface. We believe that the presence of polar sulfate groups on the particle, which initially stabilized the particle in water, reduces the adsorption of pS-b-EP. Microcapsules are formed by heating the Pickering emulsion above the glass-transition temperature of the particles. Significant aggregation is observed, if no pS-b-EP is used. The adsorption of pS-b-EP provides steric stabilization to the Pickering emulsion droplets, reduces aggregation significantly, and ultimately leads to the successful and efficient synthesis of pS microcapsules.

  15. Steric sea level change in the Bay of Bengal: investigating the most variable component of sea level change

    NASA Astrophysics Data System (ADS)

    Uebbing, Bernd; Kusche, Jürgen; Rietbroek, Roelof; Shum, Ck

    2015-04-01

    Regional sea level change is influenced by contributions from mass sources, like melting of glaciers and the ice-sheets in Greenland and Antarctica, as well as steric contributions from changes in temperature and salinity of the oceans. Radar altimetry indicates a sea level trend in the Bay of Bengal of about 6 mm- yr over the time period of 2002-2014, which is significantly larger than the global mean trend. Here, we explain 80% of this rise by steric contributions and 20% by mass-related contributions. The increased rise of sea level in the Bay of Bengal threatens the coastal vulnerability of the surrounding countries like Bangladesh, where this effect is exacerbated in combination with land subsidence of the very low lying coastal areas. The BanD-AID (Bangladesh Delta: Assessment of the Causes of Sea-level Rise Hazards and Integrated Development of Predictive Modeling Towards Mitigation and Adaptation) project tries to assess the current and future sea level rise and its impacts on the people living in the threatened coastal areas. As a part of this, it is necessary to analyze the different mass and steric contributors to the total sea level rise to aid in the prediction of future risks. We use data from radar altimetry and the GRACE mission to separate the total sea level rise into contributions from mass sources and steric changes. In our approach, temporal GRACE gravity data and Jason-1 and -2 along track altimetry data are fitted to time invariant spatial patterns (fingerprints) to avoid problems with GRACE resolution, filtering, geocenter and related issues. Our results show that in the Bay of Bengal the steric component is influenced by annual and interannual phenomena and, at the same time, it is significantly larger compared to the individual mass contributions, which show a linear and relatively stable behavior over time. We validate the steric component of our inversion by comparing it to independent steric estimates from 4-D gridded temperature and

  16. Barriers vs Creativity in Translator Training

    ERIC Educational Resources Information Center

    Yazici, Mine

    2016-01-01

    This paper discusses translation problems awaiting Turkish students as well as the creative solutions they develop in overcoming them. It consists of two parts; The first part studies the barriers concerning translation procedures from the perspective of translation theory and Turkish translation history; The second parts analyses the impact of…

  17. Barriers to Liposomal Gene Delivery: from Application Site to the Target

    PubMed Central

    Saffari, Mostafa; Moghimi, Hamid Reza; Dass, Crispin R

    2016-01-01

    Gene therapy is a therapeutic approach to deliver genetic material into cells to alter their function in entire organism. One promising form of gene delivery system (DDS) is liposomes. The success of liposome-mediated gene delivery is a multifactorial issue and well-designed liposomal systems might lead to optimized gene transfection particularly in vivo. Liposomal gene delivery systems face different barriers from their site of application to their target, which is inside the cells. These barriers include presystemic obstacles (epithelial barriers), systemic barriers in blood circulation and cellular barriers. Epithelial barriers differ depending on the route of administration. Systemic barriers include enzymatic degradation, binding and opsonisation. Both of these barriers can act as limiting hurdles that genetic material and their vector should overcome before reaching the cells. Finally liposomes should overcome cellular barriers that include cell entrance, endosomal escape and nuclear uptake. These barriers and their impact on liposomal gene delivery will be discussed in this review. PMID:28228799

  18. Calix[6]azacryptand Ligand with a Sterically Protected Tren-Based Coordination Site for Metal Ions.

    PubMed

    Zahim, Sara; Wickramasinghe, Lasantha A; Evano, Gwilherm; Jabin, Ivan; Schrock, Richard R; Müller, Peter

    2016-04-01

    A new calix[6]azacryptand ligand has been prepared in six steps starting from 1,3,5-trismethoxycalix[6]arene. An X-ray study shows that this ligand has a sterically protected tren-based binding site at the bottom of a polyaromatic bowl and ether sites around its rim. It binds Zn(2+) to give a complex in which zinc is in a trigonal bipyramidal geometry with a water bound in one apical position and two additional hydrogen-bonded waters that fill the calixarene cavity.

  19. Determining the Effective Density and Stabilizer Layer Thickness of Sterically Stabilized Nanoparticles

    PubMed Central

    2016-01-01

    A series of model sterically stabilized diblock copolymer nanoparticles has been designed to aid the development of analytical protocols in order to determine two key parameters: the effective particle density and the steric stabilizer layer thickness. The former parameter is essential for high resolution particle size analysis based on analytical (ultra)centrifugation techniques (e.g., disk centrifuge photosedimentometry, DCP), whereas the latter parameter is of fundamental importance in determining the effectiveness of steric stabilization as a colloid stability mechanism. The diblock copolymer nanoparticles were prepared via polymerization-induced self-assembly (PISA) using RAFT aqueous emulsion polymerization: this approach affords relatively narrow particle size distributions and enables the mean particle diameter and the stabilizer layer thickness to be adjusted independently via systematic variation of the mean degree of polymerization of the hydrophobic and hydrophilic blocks, respectively. The hydrophobic core-forming block was poly(2,2,2-trifluoroethyl methacrylate) [PTFEMA], which was selected for its relatively high density. The hydrophilic stabilizer block was poly(glycerol monomethacrylate) [PGMA], which is a well-known non-ionic polymer that remains water-soluble over a wide range of temperatures. Four series of PGMAx–PTFEMAy nanoparticles were prepared (x = 28, 43, 63, and 98, y = 100–1400) and characterized via transmission electron microscopy (TEM), dynamic light scattering (DLS), and small-angle X-ray scattering (SAXS). It was found that the degree of polymerization of both the PGMA stabilizer and core-forming PTFEMA had a strong influence on the mean particle diameter, which ranged from 20 to 250 nm. Furthermore, SAXS was used to determine radii of gyration of 1.46 to 2.69 nm for the solvated PGMA stabilizer blocks. Thus, the mean effective density of these sterically stabilized particles was calculated and determined to lie between 1.19 g

  20. Promoting Physical Activity: Addressing Barriers and Moving Forward

    ERIC Educational Resources Information Center

    Beighle, Aaron; Morrow, James R.

    2014-01-01

    The barriers that keep individuals from adopting and maintaining active lifestyles are very complex. Strategies for overcoming these barriers and to incentivize and assist inactive individuals to benefit from physical activity are necessary. In addition, it is important to examine the impact of public policy on active living. As youth physical…

  1. Continuing Professional Development in Australia: Barriers and Support.

    PubMed

    Summers, Anthony

    2015-08-01

    Mandatory continuing professional development (CPD) requirements for nurses are common throughout the world, with CPD being required in Australia since 2010. Many barriers to CPD have been identified. In Australia, state and territory governments have implemented supports to help nurses overcome these barriers.

  2. The Gendered International School: Barriers to Women Managers' Progression

    ERIC Educational Resources Information Center

    Sanderson, Ruth Elizabeth; Whitehead, Stephen

    2016-01-01

    Purpose: The purpose of this paper is to examine the barriers women identify to their promotion in international schools and also the ways in which women can overcome these barriers. Design/methodology/approach: The field of enquiry is international schools, with the study drawing on qualitative research. The researchers interviewed 11 women from…

  3. Sex Bias Barriers to Vocational Education Enrollment. Final Report.

    ERIC Educational Resources Information Center

    Brown, Judy Palmer; And Others

    A study was conducted to identify barriers and develop programatic strategies necessary to overcome those barriers that deter both male and female students from enrolling in vocational education programs of their choice. The study utilized a modified delphi technique to collect the perceptions of the sample groups wanting to enroll in…

  4. Designing a hydrophobic barrier within biomimetic nanopores.

    PubMed

    Trick, Jemma L; Wallace, E Jayne; Bayley, Hagan; Sansom, Mark S P

    2014-11-25

    Nanopores in membranes have a range of potential applications. Biomimetic design of nanopores aims to mimic key functions of biological pores within a stable template structure. Molecular dynamics simulations have been used to test whether a simple β-barrel protein nanopore can be modified to incorporate a hydrophobic barrier to permeation. Simulations have been used to evaluate functional properties of such nanopores, using water flux as a proxy for ionic conductance. The behavior of these model pores has been characterized as a function of pore size and of the hydrophobicity of the amino acid side chains lining the narrow central constriction of the pore. Potential of mean force calculations have been used to calculate free energy landscapes for water and for ion permeation in selected models. These studies demonstrate that a hydrophobic barrier can indeed be designed into a β-barrel protein nanopore, and that the height of the barrier can be adjusted by modifying the number of consecutive rings of hydrophobic side chains. A hydrophobic barrier prevents both water and ion permeation even though the pore is sterically unoccluded. These results both provide insights into the nature of hydrophobic gating in biological pores and channels, and furthermore demonstrate that simple design features may be computationally transplanted into β-barrel membrane proteins to generate functionally complex nanopores.

  5. How do strain and steric interactions affect the reactions of aromatic compounds with free radicals? Characterization of the radicals formed by muonium addition to p-xylene and [2.2]paracyclophane by DFT calculations and muon spin spectroscopy.

    PubMed

    McKenzie, Iain; Scheuermann, Robert; Sedlak, Kamil

    2012-07-26

    Muoniated radicals were produced by the addition of muonium (Mu) to the aromatic compound p-xylene (1) in the solid and liquid states and to the strained aromatic compound [2.2]paracyclophane (2) in the solid state. The radicals were characterized by avoided level crossing muon spin resonance spectroscopy and identified by comparing the experimentally determined muon hyperfine coupling constants with values obtained from DFT calculations. Mu was observed to add to both the secondary and tertiary carbons of 1, with the relative yield of the Mu adduct of the tertiary carbons estimated to be ∼10% in the liquid phase. The relative yield of the tertiary adduct is much higher in the solid state although this cannot be calculated exactly due to the overlap of resonances and the apparent nonuniform distribution of the radical orientations. There are three possible addition sites in 2 due to the lower symmetry of the six-membered ring compared with 1. Mu can add to the secondary carbons either from the outside of 2, generating the "exo" adduct, or from the inside, generating the "endo" adduct. The relative yields of the exo, endo, and tertiary carbon adducts are 67.1(1), 21.8(1), and 11.1(1)%, respectively. The barriers to Mu addition at the different sites of isolated molecules were determined from DFT calculations. The barriers for Mu addition to 2 are lower than the barriers for Mu addition to 1, except for addition to the "endo" position, where the unfavorable steric interactions with the second ring of 2 raise the addition barrier considerably. The measured relative yields do not reflect the distribution of products calculated using the activation energies obtained from the DFT calculations due to strong steric interactions with neighboring molecules.

  6. Nurse scientists overcoming challenges to lead transdisciplinary research teams.

    PubMed

    Kneipp, Shawn M; Gilleskie, Donna; Sheely, Amanda; Schwartz, Todd; Gilmore, Robert M; Atkinson, Daryl

    2014-01-01

    Increasingly, scientific funding agencies are requiring that researchers move toward an integrated, transdisciplinary team science paradigm. Although the barriers to and rewards of conducting this type of research have been discussed in the literature, examples of how nurse investigators have led these teams to reconcile the differences in theoretical, methodological, and/or analytic perspectives that inevitably exist are lacking. In this article, we describe these developmental trajectory challenges through a case study of one transdisciplinary team, focusing on team member characteristics and the leadership tasks associated with successful transdisciplinary science teams in the literature. Specifically, we describe how overcoming these challenges has been essential to examining the complex and potentially cumulative effects that key intersections between legal, social welfare, and labor market systems may have on the health of disadvantaged women. Finally, we discuss this difficult but rewarding work within the context of lessons learned and transdisciplinary team research in relation to the future of nursing science.

  7. Work reengineering: the benefits and the barriers, an analytical review.

    PubMed

    Murphy, R

    1995-01-01

    Hospital executives who are considering patient centered care (PCC) delivery models are undertaking a fascinating and sometimes frightening journey. Although the benefits are many, several barriers are often encountered on the way to achieving successful results. Many hospitals begin this initiative with enthusiasm and optimism because it makes so much sense. However, fear of change can set in when barriers overcome the motivation to proceed. This paper explores both the benefits and strategies for successfully overcoming the barriers. In the final analysis, each hospital's executive team must answer the call to this challenge. Their decisions hold the future of their hospital in the balance.

  8. Modeling multivalent ligand-receptor interactions with steric constraints on configurations of cell surface receptor aggregates

    SciTech Connect

    Monine, Michael; Posner, Richard; Savage, Paul; Faeder, James; Hlavacek, William S

    2008-01-01

    Signal transduction generally involves multivalent protein-protein interactions, which can produce various protein complexes and post-translational modifications. The reaction networks that characterize these interactions tend to be so large as to challenge conventional simulation procedures. To address this challenge, a kinetic Monte Carlo (KMC) method has been developed that can take advantage of a model specification in terms of reaction rules for molecular interactions. A set of rules implicitly defines the reactions that can occur as a result of the interactions represented by the rules. With the rule-based KMC method, explicit generation of the underlying chemical reaction network implied by rules is avoided. Here, we apply and extend this method to characterize the interactions of a trivalent ligand with a bivalent cell-surface receptor. This system is also studied experimentally. We consider the following kinetic models: an equivalent-site model, an extension of this model, which takes into account steric constraints on the configurations of receptor aggregates, and finally, a model that accounts for cyclic receptor aggregates. Simulation results for the equivalent-site model are consistent with an equilibrium continuum model. Using these models, we investigate the effects of steric constraints and the formation of cyclic aggregates on the kinetics and equilibria of small and large aggregate formation and the percolation phase transition that occurs in this system.

  9. Analysis of steric effects in DamID profiling of transcription factor target genes.

    PubMed

    Ramialison, Mirana; Waardenberg, Ashley J; Schonrock, Nicole; Doan, Tram; de Jong, Danielle; Bouveret, Romaric; Harvey, Richard P

    2017-03-01

    DNA adenine methyltransferase identification (DamID) is an enzymatic technology for detecting DNA regions targeted by chromatin-associated proteins. Proteins are fused to bacterial DNA adenine methyltransferase (Dam) and expressed in cultured cells or whole organisms. Here, we used DamID to detect DNA regions bound by the cardiac-restricted transcription factors (TFs) NKX2-5 and SRF, and ubiquitously-expressed co-factors ELK1 and ELK4. We compared targets bound by these TFs as N- and C-terminal fusions with Dam, for both wild type (WT) NKX2-5 and mutant proteins mimicking those found in congenital heart disease. Overall, DamID is highly robust: while the orientation of WT Dam fusions can affect the size of the target sets, their signatures remained largely reproducible. Furthermore, a severe NKX2-5 mutant lacking the homeodomain showed strong steric effects negatively impacting target discovery. The extent of steric effect is likely to be dependent on the protein in question and the orientation of Dam fusion.

  10. Structural consequences of spin conversion in a sterically encumbered Ni(II) porphyrin

    SciTech Connect

    Barkigia, K.M.; Nelson, N.Y.; Renner, M.W.; Smith, K.M.; Fajer, J.

    1999-10-14

    The crystal structure of a pyridine-ligated, high-spin Ni(II) complex of 2,3,7,8,12,13,17,18-octabromo-5, 15-bis(isopropyl)-10,20-bis(isopropylidenyl) porphyrin, is reported and compared to the unligated, low-spin Ni(II) complex previously reported. The results demonstrate that conversion to high-spin Ni(II) in nonplanar, sterically encumbered porphyrins induces a significant core expansion about the Ni while nonplanarity is still retained. The expansion of the core parameters (Ni-N, Ct-C{alpha}, Ct-Cmexo) and the Ni-N{sub axial} distances are characteristic of the d{sub x{sup 2}{minus}y{sup 2}} orbital occupancies in high-spin Ni(II) porphyrins and document the structural consequences of the spin conversion in severely nonplanar Ni(II) porphyrins. The stereochemical results are particularly relevant to ligation effects in nonplanar Ni biomolecules and synthetic porphyrins increasingly used as biomimetic models of conformational effects in chromophores and prosthetic groups in vivo, and to the remarkably wide range of lifetimes observed for excited (d,d) states in nonplanar, sterically constrained Ni(II) porphyrins in which the d{sub x{sup 2}{minus}y{sup 2}} and d{sub z{sup 2}} orbitals are also populated.

  11. Conformational effects of peripheral substituents and axial ligands in sterically crowded porphyrins

    SciTech Connect

    Nurco, D.J.; Smith, K.M.; Fajer, J.

    1997-12-31

    Crystallographic results for peripherally substituted porphyrins illustrate effects of steric crowding, axial ligation and {pi}-{pi} interactions on the structures of metalloporphyrins that begin to resemble the architectures found for porphyrinic prosthetic groups and chromophores in vivo. (1) Metalloporphyrins with multiple peripheral substituents can adopt planar, saddled, ruffled or {open_quotes}wavy{close_quotes} conformations that persist upon axial ligation of the metal. (2) In porphyrins with substituents at all peripheral positions, the substituents form pockets that force the axial ligands to align in specific orientations relative to each other and to the axes defined by the porphyrin estrogens. (3) The enforced alignment of the axial ligands caused by the substituent pocket prevents aromatic ligands from rotating around the coordination axis with intriguing consequences: the axial ligands can be forced to tip off axis because of steric crowding by adjacent molecules in the crystal lattice. (4) In porphyrins with meso substituents only, the axial ligands are free to rotate but {pi}-{pi} interactions and collacial stacking between adjacent molecules in the crystal also induce off-axis ligand tilts.

  12. Kinetic and steric differences in adsorption in two porous metal-organic frameworks

    NASA Astrophysics Data System (ADS)

    Lask, Kathleen; Krungleviciute, Vaiva; Bulut, Murat; Migone, Aldo; Lee, J.-Y.; Li, Jing

    2008-03-01

    Kinetic and steric differences are two of the three fundamental mechanisms underlying the use of adsorption in applications to gas mixture separations. We present experimental results on kinetics and equilibrium adsorption measurements of tetrafluoromethane and argon on two metal-organic framework (MOF) materials: RPM1-Co or [Co3(bpdc)3bpy].4DMF.H2O] (bpdc = biphenyldicarboxylate, bpy = 4,4'-bipyridine, DMF = N,N- dimethylformamide) and Cu-BTC or Cu3(BTC)2(H2O)3 (BTC = benzene-1,3,5-tricarboxylate). The adsorbates display significant differences in their kinetics on RPM1-Co (i.e., there are sizable differences in the time required for each gas to reach equilibrium after it is allowed access to the substrate). Our equilibrium measurements show that CF4 is sterically precluded from adsorbing in the small tetrahedral-shaped side pockets present in Cu-BTC. We will compare our experimental results with predictions for how adsorption kinetics depends on the size of the adsorbate and on those of the pores present in the substrate.

  13. Chiral assembly of weakly curled hard rods: Effect of steric chirality and polarity

    SciTech Connect

    Wensink, H. H. Morales-Anda, L.

    2015-10-14

    We theoretically investigate the pitch of lyotropic cholesteric phases composed of slender rods with steric chirality transmitted via a weak helical deformation of the backbone. In this limit, the model is amenable to analytical treatment within Onsager theory and a closed expression for the pitch versus concentration and helical shape can be derived. Within the same framework, we also briefly review the possibility of alternative types of chiral order, such as twist-bend or screw-like nematic phases, finding that cholesteric order dominates for weakly helical distortions. While long-ranged or “soft” chiral forces usually lead to a pitch decreasing linearly with concentration, steric chirality leads to a much steeper decrease of quadratic nature. This reveals a subtle link between the range of chiral intermolecular interaction and the pitch sensitivity with concentration. A much richer dependence on the thermodynamic state is revealed for polar helices where parallel and anti-parallel pair alignments along the local director are no longer equivalent. It is found that weak temperature variations may lead to dramatic changes in the pitch, despite the lyotropic nature of the assembly.

  14. Role of water and steric constraints in the kinetics of cavity–ligand unbinding

    PubMed Central

    Tiwary, Pratyush; Mondal, Jagannath; Morrone, Joseph A.; Berne, B. J.

    2015-01-01

    A key factor influencing a drug’s efficacy is its residence time in the binding pocket of the host protein. Using atomistic computer simulation to predict this residence time and the associated dissociation process is a desirable but extremely difficult task due to the long timescales involved. This gets further complicated by the presence of biophysical factors such as steric and solvation effects. In this work, we perform molecular dynamics (MD) simulations of the unbinding of a popular prototypical hydrophobic cavity–ligand system using a metadynamics-based approach that allows direct assessment of kinetic pathways and parameters. When constrained to move in an axial manner, the unbinding time is found to be on the order of 4,000 s. In accordance with previous studies, we find that the cavity must pass through a region of sharp wetting transition manifested by sudden and high fluctuations in solvent density. When we remove the steric constraints on ligand, the unbinding happens predominantly by an alternate pathway, where the unbinding becomes 20 times faster, and the sharp wetting transition instead becomes continuous. We validate the unbinding timescales from metadynamics through a Poisson analysis, and by comparison through detailed balance to binding timescale estimates from unbiased MD. This work demonstrates that enhanced sampling can be used to perform explicit solvent MD studies at timescales previously unattainable, to our knowledge, obtaining direct and reliable pictures of the underlying physiochemical factors including free energies and rate constants. PMID:26371312

  15. Evaluation of steric exclusion chromatography on cryogel column for the separation of serum proteins.

    PubMed

    Wang, Chuan; Bai, Shu; Tao, Shi-Peng; Sun, Yan

    2014-03-14

    Steric exclusion chromatography (SXC) is a new mode of protein chromatography, in which large proteins are retained on hydrophilic stationary phase surface due to the steric exclusion of polyethylene glycol (PEG) in the mobile phase, and thereafter the retained proteins can be eluted by reducing PEG concentration. In this work, SXC was evaluated on a polyacrylamide cryogel monolith. Microscopic observation of γ-globulin precipitates on the gel surface in SXC was reported for the first time. Due to the compact packing of protein precipitates on the stationary phase surface, the dynamic retention capacity of the cryogel monolith for γ-globulin reached 20 mg/mL bed volume, much higher than those of cryogel beds in adsorption-based chromatography. The effect of molecular weight and concentration of PEG, solution pH and salt concentration on protein retention capacity was in agreement with the earlier work on SXC. Because the cryogel monoliths with interconnected macropores (10-100 μm) allow much easy flow-through of viscous PEG buffer, the SXC can be operated at low back pressure. Hence, the cryogel monoliths are more suitable for SXC than other monoliths of narrow pores reported previously. In the separation of bovine serum proteins, albumin was recovered in the breakthrough fraction with high purity, and globulin was over eight times concentrated in the elution pool. This work has, thus, demonstrated the rapid serum protein separation and concentration by SXC on the cryogel monolith columns.

  16. A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers.

    PubMed

    LaBelle, James L; Katz, Samuel G; Bird, Gregory H; Gavathiotis, Evripidis; Stewart, Michelle L; Lawrence, Chelsea; Fisher, Jill K; Godes, Marina; Pitter, Kenneth; Kung, Andrew L; Walensky, Loren D

    2012-06-01

    Cancer cells subvert the natural balance between cellular life and death, achieving immortality through pathologic enforcement of survival pathways and blockade of cell death mechanisms. Pro-apoptotic BCL-2 family proteins are frequently disarmed in relapsed and refractory cancer through genetic deletion or interaction-based neutralization by overexpressed antiapoptotic proteins, resulting in resistance to chemotherapy and radiation treatments. New pharmacologic strategies are urgently needed to overcome these formidable apoptotic blockades. We harnessed the natural killing activity of BCL-2-interacting mediator of cell death (BIM), which contains one of the most potent BH3 death domains of the BCL-2 protein family, to restore BH3-dependent cell death in resistant hematologic cancers. A hydrocarbon-stapled peptide modeled after the BIM BH3 helix broadly targeted BCL-2 family proteins with high affinity, blocked inhibitory antiapoptotic interactions, directly triggered proapoptotic activity, and induced dose-responsive and BH3 sequence-specific cell death of hematologic cancer cells. The therapeutic potential of stapled BIM BH3 was highlighted by the selective activation of cell death in the aberrant lymphoid infiltrates of mice reconstituted with BIM-deficient bone marrow and in a human AML xenograft model. Thus, we found that broad and multimodal targeting of the BCL-2 family pathway can overcome pathologic barriers to cell death.

  17. Barriers to Health Care for Transgender Individuals

    PubMed Central

    Safer, Joshua D.; Coleman, Eli; Feldman, Jamie; Garofalo, Robert; Hembree, Wylie; Radix, Asa; Sevelius, Jae

    2016-01-01

    Purpose of Review Transgender persons suffer significant health disparities and may require medical intervention as part of their care. The purpose of this manuscript is to briefly review the literature characterizing barriers to health care for transgender individuals and to propose research priorities to understand mechanisms of those barriers and interventions to overcome them. Recent Findings Current research emphasizes sexual minorities’ self report of barriers, rather than using direct methods. The biggest barrier to health care reported by transgender individuals is lack of access due to lack of providers who are sufficiently knowledgeable on the topic. Other barriers include: financial barriers, discrimination, lack of cultural competence by providers, health systems barriers and socioeconomic barriers. Summary National research priorities should include rigorous determination of the capacity of the United States health care system to provide adequate care for transgender individuals. Studies should determine knowledge and biases of the medical work force across the spectrum of medical training with regard to transgender medical care; adequacy of sufficient providers for the care required, larger social structural barriers and status of a framework to pay for appropriate care. As well, studies should propose and validate potential solutions to address identified gaps. PMID:26910276

  18. Study on steric transition in asymmetrical flow field-flow fractionation and application to characterization of high-energy material.

    PubMed

    Dou, Haiyang; Lee, Yong-Ju; Jung, Euo Chang; Lee, Byung-Chul; Lee, Seungho

    2013-08-23

    In field-flow fractionation (FFF), there is the 'steric transition' phenomenon where the sample elution mode changes from the normal to steric/hyperlayer mode. Accurate analysis by FFF requires understanding of the steric transition phenomenon, particularly when the sample has a broad size distribution, for which the effect by combination of different modes may become complicated to interpret. In this study, the steric transition phenomenon in asymmetrical flow FFF (AF4) was studied using polystyrene (PS) latex beads. The retention ratio (R) gradually decreases as the particle size increases (normal mode) and reaches a minimum (Ri) at diameter around 0.5μm, after which R increases with increasing diameter (steric/hyperlayer mode). It was found that the size-based selectivity (Sd) tends to increase as the channel thickness (w) increases. The retention behavior of cyclo-1,3,5-trimethylene-2,4,6-trinitramine (commonly called 'research department explosive' (RDX)) particles in AF4 was investigated by varying experimental parameters including w and flow rates. AF4 showed a good reproducibility in size determination of RDX particles with the relative standard deviation of 4.1%. The reliability of separation obtained by AF4 was evaluated by transmission electron microscopy (TEM).

  19. Barrier Formation

    PubMed Central

    Lyaruu, D.M.; Medina, J.F.; Sarvide, S.; Bervoets, T.J.M.; Everts, V.; DenBesten, P.; Smith, C.E.; Bronckers, A.L.J.J.

    2014-01-01

    Enamel fluorosis is an irreversible structural enamel defect following exposure to supraoptimal levels of fluoride during amelogenesis. We hypothesized that fluorosis is associated with excess release of protons during formation of hypermineralized lines in the mineralizing enamel matrix. We tested this concept by analyzing fluorotic enamel defects in wild-type mice and mice deficient in anion exchanger-2a,b (Ae2a,b), a transmembrane protein in maturation ameloblasts that exchanges extracellular Cl− for bicarbonate. Defects were more pronounced in fluorotic Ae2a,b−/− mice than in fluorotic heterozygous or wild-type mice. Phenotypes included a hypermineralized surface, extensive subsurface hypomineralization, and multiple hypermineralized lines in deeper enamel. Mineral content decreased in all fluoride-exposed and Ae2a,b−/− mice and was strongly correlated with Cl−. Exposure of enamel surfaces underlying maturation-stage ameloblasts to pH indicator dyes suggested the presence of diffusion barriers in fluorotic enamel. These results support the concept that fluoride stimulates hypermineralization at the mineralization front. This causes increased release of protons, which ameloblasts respond to by secreting more bicarbonates at the expense of Cl− levels in enamel. The fluoride-induced hypermineralized lines may form barriers that impede diffusion of proteins and mineral ions into the subsurface layers, thereby delaying biomineralization and causing retention of enamel matrix proteins. PMID:24170372

  20. Addressing language barriers to healthcare in India.

    PubMed

    Narayan, Lalit

    2013-01-01

    In spite of a growing recognition of the importance of doctor-patient communication, the issue of language barriers to healthcare has received very little attention in India. The Indian population speaks over 22 major languages with English used as the lingua franca for biomedicine. Large-scale internal migration has meant that health workers are encountering increasing instances of language discordance within clinical settings. Research done predominantly in the West has shown language discordance to significantly affect access to care, cause problems of comprehension and adherence, and decrease the satisfaction and quality of care. Addressing language barriers to healthcare in India requires a stronger political commitment to providing non-discriminatory health services, especially to vulnerable groups such as illiterate migrant workers. Research will have to address three broad areas: the ways in which language barriers affect health and healthcare, the efficacy of interventions to overcome language barriers, and the costs of language barriers and efforts to overcome them. There is a need to address such barriers in health worker education and clinical practice. Proven strategies such as hiring multilingual healthcare workers, providing language training to health providers, employing in situ translators or using telephone interpretation services will have to be evaluated for their appropriateness to the Indian context. Internet-based initiatives, the proliferation of mobile phones and recent advances in machine translation promise to contribute to the solution.

  1. Overcoming Recruitment Challenges in Palliative Care Clinical Trials

    PubMed Central

    LeBlanc, Thomas W.; Lodato, Jordan E.; Currow, David C.; Abernethy, Amy P.

    2013-01-01

    Purpose: Palliative care is increasingly viewed as a necessary component of cancer care, especially for patients with advanced disease. Rigorous clinical trials are thus needed to build the palliative care evidence base, but clinical research—especially participant recruitment—is difficult. Major barriers include (1) patient factors, (2) “gatekeeping,” and (3) ethical concerns. Here we discuss an approach to overcoming these barriers, using the Palliative Care Trial (PCT) as a case study. Patients and Methods: The PCT was a 2 × 2 × 2 factorial randomized controlled trial (RCT) of different service delivery models to improve pain control in the palliative setting. It used a recruitment protocol that fused evidence-based strategies with principles of “social marketing,” an approach involving the systematic application of marketing techniques. Main components included (1) an inclusive triage algorithm, (2) information booklets targeting particular stakeholders, (3) a specialized recruitment nurse, and (4) standardization of wording across all study communications. Results: From an eligible pool of 607 patients, the PCT enrolled 461 patients over 26 months. Twenty percent of patients referred to the palliative care service were enrolled (76% of those eligible after screening). Several common barriers were minimized; among those who declined participation, family disinterest was uncommon (5%), as was the perception of burden imposed (4%). Conclusion: Challenges to clinical trial recruitment in palliative care are significant but not insurmountable. A carefully crafted recruitment and retention protocol can be effective. Our experience with designing and deploying a social-marketing–based protocol shows the benefits of such an approach. PMID:24130254

  2. Validating computer simulations of enantioselective catalysis; Reproducing the large steric and entropic contributions in Candida Antarctica lipase B

    PubMed Central

    Schopf, Patrick

    2014-01-01

    The prospect for computer aided refinement of stereoselective enzymes is further validated by simulating the ester hydrolysis by the wild type and mutants of CalB, focusing on the challenge of dealing with strong steric effects and entropic contributions. This was done using the empirical valence bond (EVB) method in a quantitative screening of the enantioselectivity, considering both kcat and kcat/KM of the R and S stereoisomers. Although the simulations require very extensive sampling for convergence they give encouraging results and major validation, indicating that our approach offers a powerful tool for computer aided design of enantioselective enzymes. This is particularly true in cases with large changes in steric effects where alternative approaches may have difficulties in capturing the interplay between steric clashes with the reacting substrate and protein flexibility. PMID:24403025

  3. African American Female College and University Presidents: Experiences and Perceptions of Barriers to the Presidency

    ERIC Educational Resources Information Center

    Jackson, Sandra; Harris, Sandra

    2007-01-01

    This study was an investigation of the experiences and perceptions of barriers to the presidency of 43 African American female college and university presidents. Findings suggested that exclusion from informal networks, lack of preparation and lack of career goals were primary barriers. Strategies to overcome these barriers included exceeding job…

  4. Steric parameters, molecular modeling and hydropathic interaction analysis of the pharmacology of para-substituted methcathinone analogues

    PubMed Central

    Sakloth, F; Kolanos, R; Mosier, P D; Bonano, J S; Banks, M L; Partilla, J S; Baumann, M H; Negus, S S; Glennon, R A

    2015-01-01

    Background and Purpose There is growing concern over the abuse of certain psychostimulant methcathinone (MCAT) analogues. This study extends an initial quantitative structure–activity relationship (QSAR) investigation that demonstrated important steric considerations of seven 4- (or para-)substituted analogues of MCAT. Specifically, the steric character (Taft's steric ES) of the 4-position substituent affected in vitro potency to induce monoamine release via dopamine and 5-HT transporters (DAT and SERT) and in vivo modulation of intracranial self-stimulation (ICSS). Here, we have assessed the effects of other steric properties of the 4-position substituents. Experimental Approach Definitive steric parameters that more explicitly focus on the volume, width and length of the MCAT 4-position substituents were assessed. In addition, homology models of human DAT and human SERT based upon the crystallized Drosophila DAT were constructed and docking studies were performed, followed by hydropathic interaction (HINT) analysis of the docking results. Key Results The potency of seven MCAT analogues at DAT was negatively correlated with the volume and maximal width of their 4-position substituents, whereas potency at SERT increased as substituent volume and length increased. SERT/DAT selectivity, as well as abuse-related drug effects in the ICSS procedure, also correlated with the same parameters. Docking solutions offered a means of visualizing these findings. Conclusions and Implications These results suggest that steric aspects of the 4-position substituents of MCAT analogues are key determinants of their action and selectivity, and that the hydrophobic nature of these substituents is involved in their potency at SERT. PMID:25522019

  5. First Davis Strait discovery overcomes offshore hazards

    SciTech Connect

    Munro, R.G.

    1982-04-01

    In spite of icebergs umpredictable currents and brief drilling seasons, the first discovery well was completed recently in the Davis Strait. The success of this well, known as Hekja 0-71, has opened the waters off the northeastern coast of Canada to more exploration. A discussion is presented of how the well was drilled, the problems encountered and how they were overcome.

  6. Overcoming the Mechanism of Radioresistance in Neuroblastoma

    DTIC Science & Technology

    2014-06-01

    of Radioresistance in Neuroblastoma PRINCIPAL INVESTIGATOR: Brian Marples PhD CONTRACTING ORGANIZATION: William Beaumont Hospital Inc...COVERED 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Overcoming the Mechanism of Radioresistance in Neuroblastoma 5b. GRANT NUMBER 5c. PROGRAM...for highly aggressive advanced-stage neuroblastoma remains poor despite a multidisciplinary approach involving aggressive surgery, chemotherapy and

  7. Successful Writing: Five Roadblocks to Overcome

    ERIC Educational Resources Information Center

    King, Kathleen P.

    2013-01-01

    This article provides essential strategies to be more successful in one of the major roles in academia: writing. Most academics struggle with roadblocks in their writing process. We are forever battling to complete research articles, manuscripts, grant proposals or other documents. The strategies and perspective shared here help overcome several…

  8. In My View. Overcoming Math Anxiety.

    ERIC Educational Resources Information Center

    Fotoples, Robert M.

    2000-01-01

    Describes math anxiety, explaining roadblocks to mathematics success; discussing strategies for overcoming anxiety (e.g., parent involvement, teacher sensitivity, and peer tutoring); and examining the influence of learning styles on mathematics achievement and attitudes. Mathematics teachers must identify students' problems in mathematics, work…

  9. Helping Developmental Students Overcome Communication Apprehension.

    ERIC Educational Resources Information Center

    Watson, Arden K.

    Since 20% of all college students experience communication apprehension (CA), the developmental student, distinguished by lower than average academic scores, may also experience this inhibiting fear of communication. Characteristics of the developmental communication apprehensive student indicate that a program for overcoming communication…

  10. Ideas for Creating and Overcoming Student Silences

    ERIC Educational Resources Information Center

    Woods, Donald R.; Sheardown, Heather

    2009-01-01

    The key idea is that 50 minutes of teacher talk with passive student listening is relatively ineffective in developing student learning. Teachers can create silences for productive active student learning. Students can also change from passive listeners to active talker-discussers of their learning. Ideas are given about how to overcome silences…

  11. Learn to Avoid or Overcome Leadership Obstacles

    ERIC Educational Resources Information Center

    D'Auria, John

    2015-01-01

    Leadership is increasingly recognized as an important factor in moving schools forward, yet we have been relatively random in how we prepare and support them. Four obstacles often block or diminish their effectiveness. Avoiding or overcoming each of these requires an underlying set of skills and knowledge that we believe can be learned and…

  12. The BARRIERS scale -- the barriers to research utilization scale: A systematic review

    PubMed Central

    2010-01-01

    Background A commonly recommended strategy for increasing research use in clinical practice is to identify barriers to change and then tailor interventions to overcome the identified barriers. In nursing, the BARRIERS scale has been used extensively to identify barriers to research utilization. Aim and objectives The aim of this systematic review was to examine the state of knowledge resulting from use of the BARRIERS scale and to make recommendations about future use of the scale. The following objectives were addressed: To examine how the scale has been modified, to examine its psychometric properties, to determine the main barriers (and whether they varied over time and geographic locations), and to identify associations between nurses' reported barriers and reported research use. Methods Medline (1991 to September 2009) and CINHAL (1991 to September 2009) were searched for published research, and ProQuest® digital dissertations were searched for unpublished dissertations using the BARRIERS scale. Inclusion criteria were: studies using the BARRIERS scale in its entirety and where the sample was nurses. Two authors independently assessed the study quality and extracted the data. Descriptive and inferential statistics were used. Results Sixty-three studies were included, with most using a cross-sectional design. Not one study used the scale for tailoring interventions to overcome identified barriers. The main barriers reported were related to the setting, and the presentation of research findings. Overall, identified barriers were consistent over time and across geographic locations, despite varying sample size, response rate, study setting, and assessment of study quality. Few studies reported associations between reported research use and perceptions of barriers to research utilization. Conclusions The BARRIERS scale is a nonspecific tool for identifying general barriers to research utilization. The scale is reliable as reflected in assessments of internal

  13. Overcoming Resistance to Culture Change: Nursing Home Administrators’ Use of Education, Training and Communication

    PubMed Central

    Tyler, Denise A.; Lepore, Michael; Shield, Renee R.; Looze, Jessica; Miller, Susan C.

    2014-01-01

    Nursing home culture change is becoming more prevalent and research has demonstrated its benefits for nursing home residents and staff, but little is known about the role of nursing home administrators in culture change implementation. The purpose of this study was to determine what barriers nursing home administrators faced in implementing culture change practices and to identify the strategies used to overcome these. We conducted in-depth individual interviews with 64 administrators identified through a nationally representative survey. Results showed that a key barrier to culture change implementation reported by administrators was staff, resident and family member resistance to change. Most nursing home administrators stressed the importance of using communication, education and training to overcome this resistance. Themes emerging around the concepts of communication and education indicate that these efforts should be ongoing, communication should be reciprocal, and that all stakeholders should be included. PMID:24266678

  14. Ethylene tri- and tetramerization: a steric parameter selectivity switch from X-ray crystallography and computational analysis.

    PubMed

    Cloete, Nicoline; Visser, Hendrik G; Engelbrecht, Ilana; Overett, Matthew J; Gabrielli, William F; Roodt, Andreas

    2013-03-04

    A steric parameter (θN-sub) is introduced to describe the steric bulk at the nitrogen atom on a range of PNP ligands used in ethylene tri- and tetramerization. This parameter was calculated for the free ligands and different metal complexes thereof and compared to catalytic data. A specific tendency is observed for the value of θN-sub and 1-hexene selectivity, and a slight increase in 1-octene selectivity is found with increased bulkiness of the substituents on the nitrogen atom.

  15. Thermodynamic control of 1,3-boratropic shifts of α- and γ-stannyl-substituted allylboranes: hyperconjugation outweighs steric effects.

    PubMed

    Stewart, Preston S; Chen, Ming; Roush, William R; Ess, Daniel H

    2011-03-18

    (E)-δ-Stannyl homoallylic alcohols are prepared by an allene hydroboration-aldehyde allylboration sequence ( Chen , M. et al. J. Am. Chem. Soc. 2010 , 132, 7881 ). Key to this reaction sequence is that the kinetic allene hydroboration product, 2a, is less stable than and isomerizes to the more sterically congested α-stannylallylborane 3a (see abstract figure). An M06-2X density functional analysis shows that the C-Sn to boron σ-π hyperconjugation interaction is sufficiently stabilizing to override the steric congestion in 3a.

  16. A steric tethering approach enables palladium-catalysed C-H activation of primary amino alcohols.

    PubMed

    Calleja, Jonas; Pla, Daniel; Gorman, Timothy W; Domingo, Victoriano; Haffemayer, Benjamin; Gaunt, Matthew J

    2015-12-01

    Aliphatic primary amines are a class of chemical feedstock essential to the synthesis of higher-order nitrogen-containing molecules, commonly found in biologically active compounds and pharmaceutical agents. New methods for the construction of complex amines remain a continuous challenge to synthetic chemists. Here, we outline a general palladium-catalysed strategy for the functionalization of aliphatic C-H bonds within amino alcohols, an important class of small molecule. Central to this strategy is the temporary conversion of catalytically incompatible primary amino alcohols into hindered secondary amines that are capable of undergoing a sterically promoted palladium-catalysed C-H activation. Furthermore, a hydrogen bond between amine and catalyst intensifies interactions around the palladium and orients the aliphatic amine substituents in an ideal geometry for C-H activation. This catalytic method directly transforms simple, easily accessible amines into highly substituted, functionally concentrated and structurally diverse products, and can streamline the synthesis of biologically important amine-containing molecules.

  17. A steric tethering approach enables palladium-catalysed C-H activation of primary amino alcohols

    NASA Astrophysics Data System (ADS)

    Calleja, Jonas; Pla, Daniel; Gorman, Timothy W.; Domingo, Victoriano; Haffemayer, Benjamin; Gaunt, Matthew J.

    2015-12-01

    Aliphatic primary amines are a class of chemical feedstock essential to the synthesis of higher-order nitrogen-containing molecules, commonly found in biologically active compounds and pharmaceutical agents. New methods for the construction of complex amines remain a continuous challenge to synthetic chemists. Here, we outline a general palladium-catalysed strategy for the functionalization of aliphatic C-H bonds within amino alcohols, an important class of small molecule. Central to this strategy is the temporary conversion of catalytically incompatible primary amino alcohols into hindered secondary amines that are capable of undergoing a sterically promoted palladium-catalysed C-H activation. Furthermore, a hydrogen bond between amine and catalyst intensifies interactions around the palladium and orients the aliphatic amine substituents in an ideal geometry for C-H activation. This catalytic method directly transforms simple, easily accessible amines into highly substituted, functionally concentrated and structurally diverse products, and can streamline the synthesis of biologically important amine-containing molecules.

  18. Steric trapping reveals a cooperativity network in the intramembrane protease GlpG

    PubMed Central

    Yang, Zhongyu; Kim, Miyeon; Sungsuwan, Suttipun; Huang, Xuefei; Hubbell, Wayne L.; Hong, Heedeok

    2016-01-01

    Membrane proteins are assembled through balanced interactions among protein, lipids and water. Studying their folding while maintaining the native lipid environment is necessary but challenging. Here we present methods for analyzing key elements in membrane protein folding including thermodynamic stability, compactness of the unfolded state and folding cooperativity under native conditions. The methods are based on steric trapping which couples unfolding of a doubly-biotinylated protein to binding of monovalent streptavidin (mSA). We further advanced this technology for general application by developing versatile biotin probes possessing spectroscopic reporters that are sensitized by mSA binding or protein unfolding. By applying these methods to an intramembrane protease GlpG of Escherichia coli, we elucidated a widely unraveled unfolded state, subglobal unfolding of the region encompassing the active site, and a network of cooperative and localized interactions to maintain the stability. These findings provide crucial insights into the folding energy landscape of membrane proteins. PMID:26999782

  19. Cryo-EM reveals the steric zipper structure of a light chain-derived amyloid fibril

    PubMed Central

    Schmidt, Andreas; Annamalai, Karthikeyan; Schmidt, Matthias; Grigorieff, Nikolaus; Fändrich, Marcus

    2016-01-01

    Amyloid fibrils are proteinaceous aggregates associated with diseases in humans and animals. The fibrils are defined by intermolecular interactions between the fibril-forming polypeptide chains, but it has so far remained difficult to reveal the assembly of the peptide subunits in a full-scale fibril. Using electron cryomicroscopy (cryo-EM), we present a reconstruction of a fibril formed from the pathogenic core of an amyloidogenic immunoglobulin (Ig) light chain. The fibril density shows a lattice-like assembly of face-to-face packed peptide dimers that corresponds to the structure of steric zippers in peptide crystals. Interpretation of the density map with a molecular model enabled us to identify the intermolecular interactions between the peptides and rationalize the hierarchical structure of the fibril based on simple chemical principles. PMID:27185936

  20. Preparation of metallic cation conducting polymers based on sterically hindered phenols containing polymeric systems

    DOEpatents

    Skotheim, T.A.; Okamoto, Yoshiyuki; Lee, H.S.

    1989-11-21

    The present invention relates to ion-conducting solvent-free polymeric systems characterized as being cationic single ion conductors. The solvent-free polymer electrolytes comprise a flexible polymer backbone to which is attached a metal salt, such as a lithium, sodium or potassium salt, of a sterically hindered phenol. The solid polymer electrolyte may be prepared either by (1) attaching the hindered phenol directly to a flexible polymeric backbone, followed by neutralization of the phenolic OH's or (2) reacting the hindered phenol with a polymer precursor which is then polymerized to form a flexible polymer having phenolic OH's which are subsequently neutralized. Preferably the hindered phenol-modified polymeric backbone contains a polyether segment. The ionic conductivity of these solvent-free polymer electrolytes has been measured to be in the range of 10[sup [minus]4] to 10[sup [minus]7] S cm[sup [minus]1] at room temperature.

  1. Preparation of metallic cation conducting polymers based on sterically hindered phenols containing polymeric systems

    DOEpatents

    Skotheim, Terje A.; Okamoto, Yoshiyuki; Lee, Hung S.

    1989-01-01

    The present invention relates to ion-conducting solvent-free polymeric systems characterized as being cationic single ion conductors. The solvent-free polymer electrolytes comprise a flexible polymer backbone to which is attached a metal salt, such as a lithium, sodium or potassium salt, of a sterically hindered phenol. The solid polymer electrolyte may be prepared either by (1) attaching the hindered phenol directly to a flexible polymeric backbone, followed by neutralization of the phenolic OH's or (2) reacting the hindered phenol with a polymer precursor which is then polymerized to form a flexible polymer having phenolic OH's which are subsequently neutralized. Preferably the hindered phenol-modified polymeric backbone contains a polyether segment. The ionic conductivity of these solvent-free polymer electrolytes has been measured to be in the range of 10.sup.-4 to 10.sup.-7 S cm.sup.-1 at room temperature.

  2. Steric modifications tune the regioselectivity of the alkane oxidation catalyzed by non-heme iron complexes.

    PubMed

    He, Yu; Gorden, John D; Goldsmith, Christian R

    2011-12-19

    Iron complexes with the tetradentate N-donor ligand N,N'-di(phenylmethyl)-N,N'-bis(2-pyridinylmethyl)-1,2-cyclohexanediamine (bbpc) are reported. Despite the benzyl groups present on the amines, the iron compounds catalyze the oxygenation of cyclohexane to an extent similar to those employing less sterically encumbered ligands. The catalytic activity is strongly dependent on the counterion, with the highest activity and the strongest preference for alkane hydroxylation correlating to the most weakly coordinating anion, SbF(6)(-). The selectivity for the alcohol product over the ketone is amplified when acetic acid is present as an additive. When hydrocarbon substrates with both secondary and tertiary carbons are oxidized by H(2)O(2), the catalyst directs oxidation toward the secondary carbons to a greater degree than other previously reported iron-containing homogeneous catalysts.

  3. A Steric Antagonism of Actin Polymerization by a Salmonella Virulence Protein

    SciTech Connect

    Margarit,S.; Davidson, W.; Frego, L.; Stebbins, F.

    2006-01-01

    Salmonella spp. require the ADP-ribosyltransferase activity of the SpvB protein for intracellular growth and systemic virulence. SpvB covalently modifies actin, causing cytoskeletal disruption and apoptosis. We report here the crystal structure of the catalytic domain of SpvB, and we show by mass spectrometric analysis that SpvB modifies actin at Arg177, inhibiting its ATPase activity. We also describe two crystal structures of SpvB-modified, polymerization-deficient actin. These structures reveal that ADP-ribosylation does not lead to dramatic conformational changes in actin, suggesting a model in which this large family of toxins inhibits actin polymerization primarily through steric disruption of intrafilament contacts.

  4. A theoretical study of steric effects in S N2 reactions

    NASA Astrophysics Data System (ADS)

    Jensen, Frank

    1992-08-01

    The gas phase reaction of chloride ion with alkyl chlorides (methyl, ethyl, propyl, i-propyl, i-butyl, t-butyl and neo-pentyl) has been studied by ab initio methods. Geometries of stationary points along the reaction coordinate have been optimized at the MP2/6-31G* level of theory and improved energies have been calculated with the 6-311 + G(2d) basis. Although all reactions are "narcissistic", i.e. reactant and product are identical, it is found that some of the transition structures have unequal CCl bond lengths. The breaking/forming CCl bond for the t-butyl system is significantly longer than for the other alkyl groups, for which the change with increasing steric bulk is as expected. The calculated relative activation energies are compared with available gas-phase data and relevant solution values.

  5. Synthesis, opioid receptor affinity, and enzymatic hydrolysis of sterically hindered morphine 3-esters.

    PubMed

    Mignat, C; Heber, D; Schlicht, H; Ziegler, A

    1996-07-01

    With the intention of preparing prodrugs, 10 morphine 3-esters were synthesized and evaluated in vitro for opioid receptor binding and enzymatic hydrolysis. The results of binding assays performed on homogenates of guinea pig brain demonstrate a loss in affinity of morphine to mu-, delta-, and kappa-receptors by esterification at the 3-position. The conversion of the esters to morphine was determined in human plasma by HPLC analysis. The half-lives of hydrolysis ranged from 0.5 to > 300 h. The investigations indicate that esterification at the 3-position results in morphine prodrugs with variable hydrolytic stability. Sterically hindered morphine 3-esters may be a promising approach to manipulate the rate of release of morphine.

  6. Development of flow/steric field-flow fractionation as a routine process control method

    SciTech Connect

    Barman, B.N.

    1988-08-30

    Researchers studied the feasibility of using the Flow/Steric Field-Flow Fractionation (Flow/StFFF) method for the characterization of particulate materials with diameters in the 1-100 micrometers range. Studies on the optimization of the method for the separation and characterization of different size particulate samples, as well as on the role of the crossflow field and channel flowrate on the separation and resolution, were performed with a number of spherical polystyrene divinylbenzene latex standards and included in the report. Applicability of the method as a fast and reliable practical tool for industrial process control, particularly for grinding operations, was examined by analyzing a number of samples obtained by grinding. Examples of materials considered include coal, limestone and glass.

  7. Enantiospecific photoresponse of sterically hindered diarylethenes for chiroptical switches and photomemories

    NASA Astrophysics Data System (ADS)

    Li, Wenlong; Li, Xin; Xie, Yongshu; Wu, Yue; Li, Mengqi; Wu, Xin-Yan; Zhu, Wei-Hong; Tian, He

    2015-03-01

    Light-driven transcription, replication and enzyme catalysis are critically dependent upon a delicate transfer between molecular and supramolecular chirality. Chemists have well realized the impressive stereospecificity over many thermally accessible cycloaddition with chiral catalysts, but making light work in the enantiomer control of diarylethene photocyclization has proved to be more challenging. Here, we report a unique sterically hindered diarylethene (BBTE) system with absolute enantiospecific photocyclization and cycloreversion. Moreover, we have fully separated all the five thermally stable isomers, consisting of one achiral parallel conformer, one pair of anti-parallel ring-open enantiomers, and another pair of ring-closed enantiomers, whose absolute chiral configurations are entirely elucidated by single X-ray crystallographic analyses. The photo-responsive feature exhibits a reversible, complete enantio-control transformation without racemism, offering an unrivaled unimolecular enantiospecific platform for potential applications as bistable chiroptical switches and all-photonic photomemories with optical rotation as non-destructive readout.

  8. Sterically stabilized liposomes as a carrier for alpha-emitting radium and actinium radionuclides.

    PubMed

    Henriksen, Gjermund; Schoultz, B W; Michaelsen, T E; Bruland, Ø S; Larsen, R H

    2004-05-01

    The alpha-particle emitting radionuclides (223)Ra (t(1/2) = 11.4 d), (224)Ra (t(1/2) = 3.6 d), and (225)Ac(t(1/2) = 10.0 d) may have a broad application in targeted radiotherapy provided that they could be linked to vehicles with tumor affinity. The potential usefulness of liposomes as carriers was studied in the present work. Radium and actinium radionuclides could be loaded in good yields into sterically stabilized liposomes. Subsequent coating of the liposomes with a folate-F(ab')(2) construct yielded a product with affinity towards tumor cells expressing folate receptors. Radionuclide loaded liposomes showed excellent stability in serum in vitro.

  9. Enantiospecific photoresponse of sterically hindered diarylethenes for chiroptical switches and photomemories

    PubMed Central

    Li, Wenlong; Li, Xin; Xie, Yongshu; Wu, Yue; Li, Mengqi; Wu, Xin-Yan; Zhu, Wei-Hong; Tian, He

    2015-01-01

    Light-driven transcription, replication and enzyme catalysis are critically dependent upon a delicate transfer between molecular and supramolecular chirality. Chemists have well realized the impressive stereospecificity over many thermally accessible cycloaddition with chiral catalysts, but making light work in the enantiomer control of diarylethene photocyclization has proved to be more challenging. Here, we report a unique sterically hindered diarylethene (BBTE) system with absolute enantiospecific photocyclization and cycloreversion. Moreover, we have fully separated all the five thermally stable isomers, consisting of one achiral parallel conformer, one pair of anti-parallel ring-open enantiomers, and another pair of ring-closed enantiomers, whose absolute chiral configurations are entirely elucidated by single X-ray crystallographic analyses. The photo-responsive feature exhibits a reversible, complete enantio-control transformation without racemism, offering an unrivaled unimolecular enantiospecific platform for potential applications as bistable chiroptical switches and all-photonic photomemories with optical rotation as non-destructive readout. PMID:25777985

  10. Optimal determination of steric mass action model parameters for beta-lactoglobulin using static batch experiments.

    PubMed

    Barz, Tilman; Löffler, Verena; Arellano-Garcia, Harvey; Wozny, Günter

    2010-06-25

    In this work, parameters of the steric mass-formalism SMA are optimally ascertained for a reliable determination of the adsorption isotherms of beta-lactoglobulin A and B under non-isocratic conditions. For this purpose, static batch experiments are used in contrast to the protocols based on different experimental steps, which use a chromatographic column. It is shown that parameters can already be determined for a small number of experiments by using a systematic procedure based on optimal model-based experimental design and an efficient NLP-solver. The in different works observed anti-Langmuir shape of the isotherm for small concentrations of beta-lactoglobulin A was corroborated. Moreover, we also found indications for a porosity variation with changing protein concentrations.

  11. Mapping the Conformational Dynamics and Pathways of Spontaneous Steric Zipper Peptide Oligomerization

    PubMed Central

    Matthes, Dirk; Gapsys, Vytautas; Daebel, Venita; de Groot, Bert L.

    2011-01-01

    The process of protein misfolding and self-assembly into various, polymorphic aggregates is associated with a number of important neurodegenerative diseases. Only recently, crystal structures of several short peptides have provided detailed structural insights into -sheet rich aggregates, known as amyloid fibrils. Knowledge about early events of the formation and interconversion of small oligomeric states, an inevitable step in the cascade of peptide self-assembly, however, remains still limited. We employ molecular dynamics simulations in explicit solvent to study the spontaneous aggregation process of steric zipper peptide segments from the tau protein and insulin in atomistic detail. Starting from separated chains with random conformations, we find a rapid formation of structurally heterogeneous, -sheet rich oligomers, emerging from multiple bimolecular association steps and diverse assembly pathways. Furthermore, our study provides evidence that aggregate intermediates as small as dimers can be kinetically trapped and thus affect the structural evolution of larger oligomers. Alternative aggregate structures are found for both peptide sequences in the different independent simulations, some of which feature characteristics of the known steric zipper conformation (e.g., -sheet bilayers with a dry interface). The final aggregates interconvert with topologically distinct oligomeric states exclusively via internal rearrangements. The peptide oligomerization was analyzed through the perspective of a minimal oligomer, i.e., the dimer. Thereby all observed multimeric aggregates can be consistently mapped onto a space of reduced dimensionality. This novel method of conformational mapping reveals heterogeneous association and reorganization dynamics that are governed by the characteristics of peptide sequence and oligomer size. PMID:21559277

  12. Schizosaccharomyces pombe kinesin-5 switches direction using a steric blocking mechanism

    PubMed Central

    Britto, Mishan; Goulet, Adeline; Rizvi, Syeda; von Loeffelholz, Ottilie; Moores, Carolyn A.

    2016-01-01

    Cut7, the sole kinesin-5 in Schizosaccharomyces pombe, is essential for mitosis. Like other yeast kinesin-5 motors, Cut7 can reverse its stepping direction, by mechanisms that are currently unclear. Here we show that for full-length Cut7, the key determinant of stepping direction is the degree of motor crowding on the microtubule lattice, with greater crowding converting the motor from minus end-directed to plus end-directed stepping. To explain how high Cut7 occupancy causes this reversal, we postulate a simple proximity sensing mechanism that operates via steric blocking. We propose that the minus end-directed stepping action of Cut7 is selectively inhibited by collisions with neighbors under crowded conditions, whereas its plus end-directed action, being less space-hungry, is not. In support of this idea, we show that the direction of Cut7-driven microtubule sliding can be reversed by crowding it with non-Cut7 proteins. Thus, crowding by either dynein microtubule binding domain or Klp2, a kinesin-14, converts Cut7 from net minus end-directed to net plus end-directed stepping. Biochemical assays confirm that the Cut7 N terminus increases Cut7 occupancy by binding directly to microtubules. Direct observation by cryoEM reveals that this occupancy-enhancing N-terminal domain is partially ordered. Overall, our data point to a steric blocking mechanism for directional reversal through which collisions of Cut7 motor domains with their neighbors inhibit their minus end-directed stepping action, but not their plus end-directed stepping action. Our model can potentially reconcile a number of previous, apparently conflicting, observations and proposals for the reversal mechanism of yeast kinesins-5. PMID:27834216

  13. Sterically stabilized gelatin microassemblies of noscapine enhance cytotoxicity, apoptosis and drug delivery in lung cancer cells.

    PubMed

    Madan, Jitender; Pandey, Ravi S; Jain, Upendra Kumar; Katare, Om P; Aneja, Ritu; Katyal, Anju

    2013-07-01

    Noscapine, recently identified as anticancer due to its microtubule-modulating properties. It is presently in Phase I/II clinical trials. The therapeutic efficacy of noscapine has been established in several xenograft models. Its pharmacokinetic limitations such as low bioavailability and high ED50 impede development of clinically relevant treatment regimens. Here we present design, synthesis, in vitro and in vivo characterization of sterically stabilized gelatin microassemblies of noscapine (SSGMS) for targeting human non-small cell lung cancer A549 cells. The average size of the sterically stabilized gelatin microassemblies of noscapine, SSGMS was 10.0±5.1 μm in comparison to noscapine-loaded gelatin microassemblies, GMS that was 8.3±5.5 μm. The noscapine entrapment efficiency of SSGMS and GMS was 23.99±4.5% and 24.23±2.6%, respectively. Prepared microassemblies were spherical in shape and did not show any drug and polymer interaction as examined by FTIR, DSC and PXRD. In vitro release data indicated that SSGMS and GMS follow first-order release kinetics and exhibited an initial burst followed by slow release of the drug. In vitro cytotoxicity evaluated using A549 cells showed a low IC50 value of SSGMS (15.5 μM) compared to GMS (30.1 μM) and free noscapine (47.2 μM). The SSGMS can facilitate a sustained therapeutic effect in terms of prolonged release of noscapine as evident by caspase-3 activity in A549 cells. Concomitantly, pharmacokinetic and biodistribution analysis showed that SSGMS increased the plasma half-life of noscapine by ~9.57-fold with an accumulation of ~48% drug in the lungs. Our data provides evidence for the potential usefulness of SSGMS for noscapine delivery in lung cancer.

  14. Anti-amyloid precursor protein immunoglobulins inhibit amyloid-β production by steric hindrance.

    PubMed

    Thomas, Rhian S; Liddell, J Eryl; Kidd, Emma J

    2011-01-01

    The cleavage of amyloid precursor protein (APP) by β- and γ-secretases results in the production of amyloid-β (Aβ) in Alzheimer's disease. We raised two monoclonal antibodies, 2B3 and 2B12, that recognize the β-secretase cleavage site on APP but not Aβ. We hypothesized that these antibodies would reduce Aβ levels via steric hindrance of β-secretase. Both antibodies decreased extracellular Aβ levels from astrocytoma cells, but 2B3 was more potent than 2B12. Levels of soluble sAPPα from the nonamyloidogenic α-secretase pathway and intracellular APP were not affected by either antibody nor were there any effects on cell viability. 2B3 exhibited a higher affinity for APP than 2B12 and its epitope appeared to span the cleavage site, whereas 2B12 bound slightly upstream. Both of these factors probably contribute to its greater effect on Aβ levels. After 60 min incubation at pH 4.0, most 2B3 and 2B12 remained bound to their antigen, suggesting that the antibodies will remain bound to APP in the acidic endosomes where β-secretase cleavage probably occurs. Only 2B3 and 2B12, but not control antibodies, inhibited the cleavage of sAPPα by β-secretase in a cell-free assay where the effects of antibody internalization and intracellular degradation were excluded. 2B3 virtually abolished this cleavage. In addition, levels of C-terminal APP fragments, generated following β-secretase cleavage (βCTF), were significantly reduced in cells after incubation with 2B3. These results strongly suggest that anti-cleavage site IgGs can generically reduce Aβ levels via inhibition of β-secretase by steric hindrance and may provide a novel alternative therapy for Alzheimer's disease.

  15. Targeted Sterically Stabilized Phospholipid siRNA Nanomedicine for Hepatic and Renal Fibrosis

    PubMed Central

    Khaja, Fatima; Jayawardena, Dulari; Kuzmis, Antonina; Önyüksel, Hayat

    2016-01-01

    Since its discovery, small interfering RNA (siRNA) has been considered a potent tool for modulating gene expression. It has the ability to specifically target proteins via selective degradation of messenger RNA (mRNA) not easily accessed by conventional drugs. Hence, RNA interference (RNAi) therapeutics have great potential in the treatment of many diseases caused by faulty protein expression such as fibrosis and cancer. However, for clinical application siRNA faces a number of obstacles, such as poor in vivo stability, and off-target effects. Here we developed a unique targeted nanomedicine to tackle current siRNA delivery issues by formulating a biocompatible, biodegradable and relatively inexpensive nanocarrier of sterically stabilized phospholipid nanoparticles (SSLNPs). This nanocarrier is capable of incorporating siRNA in its core through self-association with a novel cationic lipid composed of naturally occuring phospholipids and amino acids. This overall assembly protects and delivers sufficient amounts of siRNA to knockdown over-expressed protein in target cells. The siRNA used in this study, targets connective tissue growth factor (CTGF), an important regulator of fibrosis in both hepatic and renal cells. Furthermore, asialoglycoprotein receptors are targeted by attaching the galactosamine ligand to the nanocarries which enhances the uptake of nanoparticles by hepatocytes and renal tubular epithelial cells, the major producers of CTGF in fibrosis. On animals this innovative nanoconstruct, small interfering RNA in sterically stabilized phospholipid nanoparticles (siRNA-SSLNP), showed favorable pharmacokinetic properties and accumulated mostly in hepatic and renal tissues making siRNA-SSLNP a suitable system for targeting liver and kidney fibrotic diseases.

  16. Steric and electronic effects on the configurational stability of residual chiral phosphorus-centered three-bladed propellers: tris-aryl phosphane oxides.

    PubMed

    Benincori, Tiziana; Bonometti, Valentina; Cirilli, Roberto; Mussini, Patrizia R; Marchesi, Andrea; Pierini, Marco; Pilati, Tullio; Rizzo, Simona; Sannicolò, Francesco

    2013-01-02

    A series of tris-aryl phosphane oxides existing as residual enantiomers or diastereoisomers with substituents on the aryl rings differing in size and electronic properties were synthesized and characterized. Their electronic properties were evaluated on the basis of their electrochemical oxidation and reduction potentials together with those of the corresponding "blade bromides" (i.e., the naphthalene derivatives displaying the same substitution pattern of the tris-naphthyl phosphane oxide blades, with a bromo substituent where the phosphorus atom is located) determined by CV. The residual stereoisomeric phosphane oxides were isolated in a stereochemically pure state and were found to be highly configurationally stable at room temperature (stereoisomerization barriers of about 27 kcal mol(-1)). The chiroptical properties of the residual stereoisomers and the assignments of absolute configuration are discussed. The configurational stability of residual tris-aryl phosphane oxides was found to be scarcely influenced by the electronic properties of the substituents present on the aromatic rings constituting the blades, while steric effects play the most relevant role. Detailed theoretical calculations are in agreement with the experimental results and also contribute to a rational interpretation of the stereodynamics of these systems.

  17. Overcoming drug resistance through in silico prediction.

    PubMed

    Carbonell, Pablo; Trosset, Jean-Yves

    2014-03-01

    Prediction tools are commonly used in pre-clinical research to assist target selection, to optimize drug potency or to predict the pharmacological profile of drug candidates. In silico prediction and overcoming drug resistance is a new opportunity that creates a high interest in pharmaceutical research. This review presents two main in silico strategies to meet this challenge: a structure-based approach to study the influence of mutations on the drug-target interaction and a system-biology approach to identify resistance pathways for a given drug. In silico screening of synergies between therapeutic and resistant pathways through biological network analysis is an example of technique to escape drug resistance. Structure-based drug design and in silico system biology are complementary approaches to reach few objectives at once: increase efficiency, reduce toxicity and overcoming drug resistance.

  18. [Overcoming mandatory vaccination policy: first steps].

    PubMed

    Ferro, A; Cinquetti, S; Menegon, T; Napoletano, G; Bertoncello, L; Valsecchi, M

    2008-01-01

    Steps toward overcoming mandatory vaccination policy follow two main tracks: scientific and administrative. Scientific course checks starting conditions of the project in Veneto Region and monitors the effects of policy. Thanks to sensibilization regional programs and partecipation to national campaigns of vaccination, Veneto Region has achieved high coverage for all actively promoted vaccinations. Specific projects has been implemented in order to improve vaccination system quality, particularly with regard to infectious diseases and vaccine adverse events surveillance, training workers and informatization. On 23rd March 2007 Veneto Region passed the regional law number 7 called "Sospensione dell'obbligo vaccinale per l'età evolutiva" becoming in force for children born since January 1st 2008. The law provides for the institution of a scientific committee having the task of monitoring both vaccination coverage and preventable infectious diseases incidence after overcoming mandatory vaccination policy.

  19. Evaluating Depth-Integrated Steric Contributions to Sea-Level Trends and Variability in Earth System Model Ensembles

    NASA Astrophysics Data System (ADS)

    Hogan, E.; Sriver, R. L.

    2015-12-01

    Earth system model ensembles exhibit considerable uncertainties surrounding trends and magnitude of steric sea-level variations, due in part to structural model differences, internal model variability, and parameterizations that influence ocean heat uptake. Here we analyze depth-integrated steric sea-level changes using the CMIP5 models and a new CESM ensemble that samples internal variability of the coupled Earth system. The CESM ensemble contains 50 members, with historical and future projections (1850-2100) initialized from unique model states sampled from a ~10,000 year fully coupled unforced equilibrium simulation. The CESM ensemble enables us to examine how initial conditions uncertainty (internal variability) within the full-ocean can influence depth-integrated steric sea-level variability. The second ensemble is comprised of runs from 32 different CMIP5 models. We performed grid-level drift correction for each model using the pre-industrial control simulations, which enables us to examine depth-integrated variability and trends due to different model structures. We compare and contrast our results with published observational datasets, and we analyze the effect of different sources of uncertainty on simulated sea-level variability and trends for different ocean depths. Results point to the importance of the deep ocean in attempting to attribute and predict temporal patterns of steric sea-level on a global scale.

  20. Direct imaging of the structure, relaxation, and sterically constrained motion of encapsulated tungsten polyoxometalate lindqvist ions within carbon nanotubes.

    PubMed

    Sloan, Jeremy; Matthewman, Gemma; Dyer-Smith, Clare; Sung, A-Young; Liu, Zheng; Suenaga, Kazu; Kirkland, Angus I; Flahaut, Emmanuel

    2008-05-01

    The imaging properties and observation of the sterically regulated translational motion of discrete tungsten polyoxometalate Linqvist ions (i.e., [W(6)O(19)](2-)) within carbon nanotubes of specific internal diameter are reported. The translational motion of the nonspheroidal anion within the nanotube capillary is found to be impeded by its near-perfect accommodation to the internal van der Waals surface of the nanotube wall. Rotational motion of the anion about one remaining degree of freedom permits translational motion of the anion along the nanotube followed by locking in at sterically favorable positions in a mechanism similar to a molecular ratchet. This steric locking permits the successful direct imaging of the constituent octahedral cation template of individual [W(6)O(19)](2-) anions by high resolution transmission electron microscopy thereby permitting meterological measurements to be performed directly on the anion. Direct imaging of pairs of equatorial W(2) atoms within the anion reveal steric relaxation of the anion contained within the nanotube capillary relative to the bulk anion structure.

  1. Comment on "Rabbit-Ears Hybrids, VSEPR Sterics, and Other Orbital Anachronisms": A Reply to a Criticism

    ERIC Educational Resources Information Center

    Hiberty, Philippe C.; Danovich, David; Shaik, Sason

    2015-01-01

    This commentary summarizes the authors' basic disagreements with the paper, "Rabbit-Ears, VSEPR Sterics, and Other Orbital Anachronisms," which criticizes the authors' usage of the hybrid orbitals for H[subscript 2]O in their book, "A Chemist's Guide to Valence Bond Theory" (Shaik and Hiberty, 2008). The current article shows…

  2. [Cancer immunotherapy. Importance of overcoming immune suppression].

    PubMed

    Malvicini, Mariana; Puchulo, Guillermo; Matar, Pablo; Mazzolini, Guillermo

    2010-01-01

    Increasing evidence indicates that the immune system is involved in the control of tumor progression. Effective antitumor immune response depends on the interaction between several components of the immune system, including antigen-presenting cells and different T cell subsets. However, tumor cells develop a number of mechanisms to escape recognition and elimination by the immune system. In this review we discuss these mechanisms and address possible therapeutic approaches to overcome the immune suppression generated by tumors.

  3. Glycoprotein mucin molecular brush on cancer cell surface acting as mechanical barrier against drug delivery

    NASA Astrophysics Data System (ADS)

    Wang, Xin; Shah, Aalok A.; Campbell, Robert B.; Wan, Kai-tak

    2010-12-01

    Uptake of cytotoxic drugs by typical tumor cells is limited by the dense dendritic network of oligosaccharide mucin chains that forms a mechanical barrier. Atomic force microscopy is used to directly measure the force needed to pierce the mucin layer to reach the cell surface. Measurements are analyzed by de Gennes' steric reptation theory. Multidrug resistant ovarian tumor cells shows significantly larger penetration load compared to the wide type. A pool of pancreatic, lung, colorectal, and breast cells are also characterized. The chemotherapeutic agent, benzyl-α-GalNac, for inhibiting glycosylation is shown to be effective in reducing the mechanical barrier.

  4. Strong steric hindrance effect on excited state structural dynamics of Cu(I) diimine complexes.

    PubMed

    Gothard, Nosheen A; Mara, Michael W; Huang, Jier; Szarko, Jodi M; Rolczynski, Brian; Lockard, Jenny V; Chen, Lin X

    2012-03-08

    The metal-to-ligand-charge-transfer (MLCT) excited state of Cu(I) diimine complexes is known to undergo structural reorganization, transforming from a pseudotetrahedral D(2d) symmetry in the ground state to a flattened D(2) symmetry in the MLCT state, which allows ligation with a solvent molecule, forming an exciplex intermediate. Therefore, the structural factors that influence the coordination geometry change and the solvent accessibility to the copper center in the MLCT state could be used to control the excited state properties. In this study, we investigated an extreme case of the steric hindrance caused by attaching bulky tert-butyl groups in bis(2,9-di-tert-butyl-1,10-phenanthroline)copper(I), [Cu(I)(dtbp)(2)](+). The two bulky tert-butyl groups on the dtbp ligand lock the MLCT state into the pseudotetrahedral coordination geometry and completely block the solvent access to the copper center in the MLCT state of [Cu(I)(dtbp)(2)](+). Using ultrafast transient absorption spectroscopy and time-resolved emission spectroscopy, we investigated the MLCT state property changes due to the steric hindrance and demonstrated that [Cu(I)(dtbp)(2)](+) exhibited a long-lived emission but no subpicosecond component that was previously assigned as the flattening of the pseudotetrahedral coordination geometry. This suggests the retention of its pseudotetrahedral D(2d) symmetry and the blockage of the solvent accessibility. We made a comparison between the excited state dynamics of [Cu(I)(dtbp)(2)](+) with its mono-tert-butyl counterpart, bis(2-tert-butyl-1,10-phenanthroline)copper(I) [Cu(I)(tbp)(2)](+). The subpicosecond component assigned to the flattening of the D(2d) coordination geometry in the MLCT excited state was again present in the latter because the absence of a tert-butyl on the phenanthroline allows flattening to the pseudotetrahedral coordination geometry. Unlike the [Cu(I)(dtbp)(2)](+), [Cu(I)(tbp)(2)](+) exhibited no detectable emission at room temperature in

  5. Unusually Efficient Pyridine Photodissociation from Ru(II) Complexes with Sterically Bulky Bidentate Ancillary Ligands

    PubMed Central

    2015-01-01

    The introduction of steric bulk to the bidentate ligand in [Ru(tpy)(bpy)(py)]2+ (1; tpy = 2,2′:2′,6″-terpyridine; bpy = 2,2′-bipyridine; py = pyridine) to provide [Ru(tpy)(Me2bpy)(py)]2+ (2; Me2bpy = 6,6′-dimethyl-2,2′-bipyridine) and [Ru(tpy)(biq)(py)]2+ (3; biq = 2,2′-biquinoline) facilitates photoinduced dissociation of pyridine with visible light. Upon irradiation of 2 and 3 in CH3CN (λirr = 500 nm), ligand exchange occurs to produce the corresponding [Ru(tpy)(NN)(NCCH3)]2+ (NN = Me2bpy, biq) complex with quantum yields, Φ500, of 0.16(1) and 0.033(1) for 2 and 3, respectively. These values represent an increase in efficiency of the reaction by 2–3 orders of magnitude as compared to that of 1, Φ500 < 0.0001, under similar experimental conditions. The photolysis of 2 and 3 in H2O with low energy light to produce [Ru(tpy)(NN)(OH2)]2+ (NN = Me2bpy, biq) also proceeds rapidly (λirr > 590 nm). Complexes 1–3 are stable in the dark in both CH3CN and H2O under similar experimental conditions. X-ray crystal structures and theoretical calculations highlight significant distortion of the planes of the bidentate ligands in 2 and 3 relative to that of 1. The crystallographic dihedral angles defined by the bidentate ligand, Me2bpy in 2 and biq in 3, and the tpy ligand were determined to be 67.87° and 61.89°, respectively, whereas only a small distortion from the octahedral geometry is observed between bpy and tpy in 1, 83.34°. The steric bulk afforded by Me2bpy and biq also result in major distortions of the pyridine ligand in 2 and 3, respectively, relative to 1, which are believed to weaken its σ-bonding and π-back-bonding to the metal and play a crucial role in the efficiency of the photoinduced ligand exchange. The ability of 2 and 3 to undergo ligand exchange with λirr > 590 nm makes them potential candidates to build photochemotherapeutic agents for the delivery of drugs with pyridine binding groups. PMID:25027458

  6. Stereoelectronic and steric effects in the collagen triple helix: toward a code for strand association.

    PubMed

    Hodges, Jonathan A; Raines, Ronald T

    2005-11-16

    Collagen is the most abundant protein in animals. The protein consists of a helix of three strands, each with sequence X-Y-Gly. Natural collagen is most stable when X is (2S)-proline (Pro) and Y is (2S,4R)-4-hydroxyproline (4R-Hyp). We had shown previously that triple helices in which X is (2S,4S)-4-fluoroproline (4S-Flp) or Y is (2S,4R)-4-fluoroproline (4R-Flp) display hyperstability. This hyperstability arises from stereoelectronic effects that preorganize the main-chain dihedral angles in the conformation found in the triple helix. Here, we report the synthesis of strands containing both 4S-Flp in the X-position and 4R-Flp in the Y-position. We find that these strands do not form a stable triple helix, presumably because of an unfavorable steric interaction between fluoro groups on adjacent strands. Density functional theory calculations indicate that (2S,3S)-3-fluoroproline (3S-Flp), like 4S-Flp, should preorganize the main chain properly for triple-helix formation but without a steric conflict. Synthetic strands containing 3S-Flp in the X-position and 4R-Flp in the Y-position do form a triple helix. This helix is, however, less stable than one with Pro in the X-position, presumably because of an unfavorable inductive effect that diminishes the strength of the interstrand 3S-FlpC=O...H-NGly hydrogen bond. Thus, other forces can counter the benefits derived from the proper preorganization. Although (Pro-Pro-Gly)7 and (4S-Flp-4R-Flp-Gly)7 do not form stable homotrimeric helices, mixtures of these two peptides form stable heterotrimeric helices containing one (Pro-Pro-Gly)7 strand and two (4S-Flp-4R-Flp-Gly)7 strands. This stoichiometry can be understood by considering the cross sections of the two possible heterotrimeric helices. This unexpected finding portends the development of a "code" for the self-assembly of determinate triple helices from two or three strands.

  7. Unusually efficient pyridine photodissociation from Ru(II) complexes with sterically bulky bidentate ancillary ligands.

    PubMed

    Knoll, Jessica D; Albani, Bryan A; Durr, Christopher B; Turro, Claudia

    2014-11-13

    The introduction of steric bulk to the bidentate ligand in [Ru(tpy)(bpy)(py)](2+) (1; tpy = 2,2':2',6″-terpyridine; bpy = 2,2'-bipyridine; py = pyridine) to provide [Ru(tpy)(Me2bpy)(py)](2+) (2; Me2bpy = 6,6'-dimethyl-2,2'-bipyridine) and [Ru(tpy)(biq)(py)](2+) (3; biq = 2,2'-biquinoline) facilitates photoinduced dissociation of pyridine with visible light. Upon irradiation of 2 and 3 in CH3CN (λirr = 500 nm), ligand exchange occurs to produce the corresponding [Ru(tpy)(NN)(NCCH3)](2+) (NN = Me2bpy, biq) complex with quantum yields, Φ500, of 0.16(1) and 0.033(1) for 2 and 3, respectively. These values represent an increase in efficiency of the reaction by 2-3 orders of magnitude as compared to that of 1, Φ500 < 0.0001, under similar experimental conditions. The photolysis of 2 and 3 in H2O with low energy light to produce [Ru(tpy)(NN)(OH2)](2+) (NN = Me2bpy, biq) also proceeds rapidly (λirr > 590 nm). Complexes 1-3 are stable in the dark in both CH3CN and H2O under similar experimental conditions. X-ray crystal structures and theoretical calculations highlight significant distortion of the planes of the bidentate ligands in 2 and 3 relative to that of 1. The crystallographic dihedral angles defined by the bidentate ligand, Me2bpy in 2 and biq in 3, and the tpy ligand were determined to be 67.87° and 61.89°, respectively, whereas only a small distortion from the octahedral geometry is observed between bpy and tpy in 1, 83.34°. The steric bulk afforded by Me2bpy and biq also result in major distortions of the pyridine ligand in 2 and 3, respectively, relative to 1, which are believed to weaken its σ-bonding and π-back-bonding to the metal and play a crucial role in the efficiency of the photoinduced ligand exchange. The ability of 2 and 3 to undergo ligand exchange with λirr > 590 nm makes them potential candidates to build photochemotherapeutic agents for the delivery of drugs with pyridine binding groups.

  8. Pharmacokinetics and therapeutics of sterically stabilized liposomes in mice bearing C-26 colon carcinoma.

    PubMed

    Huang, S K; Mayhew, E; Gilani, S; Lasic, D D; Martin, F J; Papahadjopoulos, D

    1992-12-15

    Three different liposome types were compared for blood clearance and tissue uptake in mice bearing C-26 colon carcinoma growing either s.c. or in liver. Therapeutic experiments were performed with the liposome preparation showing the highest tumor uptake. Liposomes were composed of solid-phase phosphatidylcholine, either distearoyl phosphatidylcholine or hydrogenated soy phosphatidylcholine, and cholesterol at a 2:1 molar ratio. These liposomes were compared with similar but sterically stabilized liposomes (SL) which, in addition, contained either GM1 ganglioside or phosphatidylethanolamine derivatized with poly(ethylene glycol). Pharmacokinetic analysis of drug disposition was based on the areas under the curve for liposome-entrapped 67Ga uptake per gram of tissue up to 96 h following i.v. injection. The highest tissue area under the curve values with both liposome types were obtained in spleen, liver, and tumor. However, the sterically stabilized liposomes gave an area under the curve value 2-3-fold higher in the s.c. tumor and about 2-fold lower in liver and spleen. The therapeutic efficacy of doxorubicin (DOX) and epirubicin (EPI) encapsulated in poly(ethylene glycol)-derivatized phosphatidylethanolamine-containing liposomes was compared with that of free drug at two doses, 6 and 9 (or 10) mg/kg animal weight. Liposomes containing drug were injected either as a single dose, at different times following tumor implantation, or as three weekly doses starting 10 days after implantation. When injected as a single dose, liposome-encapsulated DOX had the maximal effect on tumor growth when injected 6 to 9 days after tumor implantation. When injected as three weekly doses, with treatment starting with a delay of 10 days, tumors which had grown to a size of approximately 0.05-0.1 cm3 regressed in groups of animals treated with either liposome-encapsulated drug (SL-DOX or SL-EPI) but continued to grow unabated in untreated mice and in mice receiving either of the free

  9. Unlocking the steric gate of DNA polymerase η leads to increased genomic instability in Saccharomyces cerevisiae

    PubMed Central

    Donigan, Katherine A.; Cerritelli, Susana M.; McDonald, John P.; Vaisman, Alexandra; Crouch, Robert J.; Woodgate, Roger

    2015-01-01

    DNA polymerase η (pol η) is best characterized for its ability to perform accurate and efficient translesion DNA synthesis (TLS) through cyclobutane pyrimidine dimers (CPDs). To ensure accurate bypass the polymerase is not only required to select the correct base, but also discriminate between NTPs and dNTPs. Most DNA polymerases have a conserved “steric gate” residue which functions to prevent incorporation of NMPs during DNA synthesis. Here, we demonstrate that the Phe35 residue of S. cerevisiae pol η functions as a steric gate to limit the use of ribonucleotides during polymerization both in vitro and in vivo. Unlike the related polι enzyme, wild-type pol η does not readily incorporate NMPs in vitro. In contrast, a pol η F35A mutant incorporates NMPs on both damaged and undamaged DNA in vitro with a high degree of base selectivity. An S. cerevisiae strain expressing pol η F35A (rad30-F35A) that is also deficient for nucleotide excision repair (rad1Δ) and the TLS polymerase, pol ζ (rev3Δ), is extremely sensitive to UV-light. The sensitivity is due, in part, to RNaseH2 activity, as an isogenic rnh201Δ strain is roughly 50-fold more UV-resistant than its RNH201+ counterpart. Interestingly the rad1Δ rev3Δ rad30-F35A rnh201Δ strain exhibits a significant increase in the extent of spontaneous mutagenesis with a spectrum dominated by 1 bp deletions at runs of template Ts. We hypothesize that the increased mutagenesis is due to rA incorporation at these sites and that the short poly rA tract is subsequently repaired in an error-prone manner by a novel repair pathway that is specifically targeted to polyribonucleotide tracks. These data indicate that under certain conditions, pol η can compete with the cell’s replicases and gain access to undamaged genomic DNA. Such observations are consistent with a role for pol η in replicating common fragile sites (CFS) in human cells. PMID:26340535

  10. Strategies to Overcome Heparins’ Low Oral Bioavailability

    PubMed Central

    Neves, Ana Rita; Correia-da-Silva, Marta; Sousa, Emília; Pinto, Madalena

    2016-01-01

    Even after a century, heparin is still the most effective anticoagulant available with few side effects. The poor oral absorption of heparins triggered the search for strategies to achieve oral bioavailability since this route has evident advantages over parenteral administration. Several approaches emerged, such as conjugation of heparins with bile acids and lipids, formulation with penetration enhancers, and encapsulation of heparins in micro and nanoparticles. Some of these strategies appear to have potential as good delivery systems to overcome heparin’s low oral bioavailability. Nevertheless, none have reached the market yet. Overall, this review aims to provide insights regarding the oral bioavailability of heparin. PMID:27367704

  11. Overcoming semantic heterogeneity in spatial data infrastructures

    NASA Astrophysics Data System (ADS)

    Lutz, M.; Sprado, J.; Klien, E.; Schubert, C.; Christ, I.

    2009-04-01

    In current spatial data infrastructures (SDIs), it is still often difficult to effectively exchange or re-use geographic data sets. A main reason for this is semantic heterogeneity, which occurs at different levels: at the metadata, the schema and the data content level. It is the goal of the work presented in this paper to overcome the problems caused by semantic heterogeneity on all three levels. We present a method based on ontologies and logical reasoning, which enhances the discovery, retrieval, interpretation and integration of geographic data in SDIs. Its benefits and practical use are illustrated with examples from the domains of geology and hydrology.

  12. The interaction of sterically stabilized magnetic nanoparticles with fresh human red blood cells

    PubMed Central

    Pham, Binh TT; Jain, Nirmesh; Kuchel, Philip W; Chapman, Bogdan E; Bickley, Stephanie A; Jones, Stephen K; Hawkett, Brian S

    2015-01-01

    Sterically stabilized superparamagnetic iron oxide nanoparticles (SPIONs) were incubated with fresh human erythrocytes (red blood cells [RBCs]) to explore their potential application as magnetic resonance imaging contrast agents. The chemical shift and linewidth of 133Cs+ resonances from inside and outside the RBCs in 133Cs nuclear magnetic resonance spectra were monitored as a function of time. Thus, we investigated whether SPIONs of two different core sizes and with three different types of polymeric stabilizers entered metabolically active RBCs, consuming glucose at 37°C. The SPIONs broadened the extracellular 133Cs+ nuclear magnetic resonance, and brought about a small change in its chemical shift to a higher frequency; while the intracellular resonance remained unchanged in both amplitude and chemical shift. This situation pertained over incubation times of up to 90 minutes. If the SPIONs had entered the RBCs, the intracellular resonance would have become broader and possibly even shifted. Therefore, we concluded that our SPIONs did not enter the RBCs. In addition, the T2 relaxivity of the small and large particles was 368 and 953 mM−1 s−1, respectively (three and nine times that of the most effective commercially available samples). This suggests that these new SPIONs will provide a superior performance to any others reported thus far as magnetic resonance imaging contrast agents. PMID:26604741

  13. Gauche effect in 1,2-difluoroethane. Hyperconjugation, bent bonds, steric repulsion.

    PubMed

    Goodman, Lionel; Gu, Hongbing; Pophristic, Vojislava

    2005-02-17

    Natural bond orbital deletion calculations show that whereas the gauche preference arises from vicinal hyperconjugative interaction between anti C-H bonds and C-F* antibonds, the cis C-H/C-F* interactions are substantial (approximately 25% of the anti interaction). The established significantly >60 degrees FCCF dihedral angle for the equilibrium conformer can then be rationalized in terms of the hyperconjugation model alone by taking into account both anti interactions that maximize near 60 degrees and the smaller cis interactions that maximize at a much larger dihedral angle. This explanation does not invoke repulsive forces to rationalize the 72 degrees equilibrium conformer angle. The relative minimum energy for the trans conformer is the consequence of a balance between decreasing hyperconjugative stabilization and decreasing steric destabilization as the FCCF torsional angle approaches 180 degrees . The torsional coordinate is predicted to be strongly contaminated by CCF bending, with the result that approximately half of the trans --> gauche stabilization energy stems from mode coupling.

  14. Steric confinement and enhanced local flexibility assist knotting in simple models of protein folding.

    PubMed

    Soler, Miguel A; Rey, Antonio; Faísca, Patrícia F N

    2016-09-29

    The chaperonin complex GroEL-GroES is able to accelerate the folding process of knotted proteins considerably. However, the folding mechanism inside the chaperonin cage is elusive. Here we use a combination of lattice and off-lattice Monte Carlo simulations of simple Gō models to study the effect of physical confinement and local flexibility on the folding process of protein model systems embedding a trefoil knot in their native structure. This study predicts that steric confinement plays a specific role in the folding of knotted proteins by increasing the knotting probability for very high degrees of confinement. This effect is observed for protein MJ0366 even above the melting temperature for confinement sizes compatible with the size of the GroEL/GroES chaperonin cage. An enhanced local flexibility produces the same qualitative effects on the folding process. In particular, we observe that knotting probability increases up to 40% in the transition state of protein MJ0366 when flexibility is enhanced. This is underlined by a structural change in the transition state, which becomes devoid of helical content. No relation between the knotting mechanism and flexibility was found in the context of the off-lattice model adopted in this work.

  15. Evidence that regulatory protein MarA of Escherichia coli represses rob by steric hindrance.

    PubMed

    McMurry, Laura M; Levy, Stuart B

    2010-08-01

    The MarA protein of Escherichia coli can both activate and repress the initiation of transcription, depending on the position and orientation of its degenerate 20-bp binding site ("marbox") at the promoter. For all three known repressed genes, the marbox overlaps the promoter. It has been reported that MarA represses the rob promoter via an RNA polymerase (RNAP)-DNA-MarA ternary complex. Under similar conditions, we found a ternary complex for the repressed purA promoter also. These findings, together with the backwards orientation of repressed marboxes, suggested a unique interaction of MarA with RNAP in repression. However, no repression-specific residues of MarA could be found among 38 single-alanine replacement mutations previously shown to retain activation function or among mutants from random mutagenesis. Mutations Thr12Ala, Arg36Ala, Thr95Ile, and Pro106Ala were more damaging for activation than for repression, some up to 10-fold, so these residues may play a specific role in activation. We found that nonspecific binding of RNAP to promoterless regions of DNA was presumably responsible for the ternary complexes seen previously. When RNAP binding was promoter specific, MarA reduced RNAP access to the rob promoter; there was little or no ternary complex. These findings strongly implicate steric hindrance as the mechanism of repression of rob by MarA.

  16. Grafting zwitterionic polymer onto cryogel surface enhances protein retention in steric exclusion chromatography on cryogel monolith.

    PubMed

    Tao, Shi-Peng; Zheng, Jie; Sun, Yan

    2015-04-10

    Cryogel monoliths with interconnected macropores (10-100μm) and hydrophilic surfaces can be employed as chromatography media for protein retention in steric exclusion chromatography (SXC). SXC is based on the principle that the exclusion of polyethylene glycol (PEG) on both a hydrophilic chromatography surface and a protein favors their association, leading to the protein retention on the chromatography surface. Elution of the retained protein can be achieved by reducing PEG concentration. In this work, the surface of polyacrylamide-based cryogel monolith was modified by grafting zwitterionic poly(carboxybetaine methacrylate) (pCBMA), leading the increase in the surface hydrophilicity. Observation by scanning electron microscopy revealed the presence of the grafted pCBMA chain clusters on the cryogel surface, but pCBMA grafting did not result in the changes of the physical properties of the monolith column, and the columns maintained good recyclability in SXC. The effect of the surface grafting on the SXC behavior of γ-globulin was investigated in a wide flow rate range (0.6-12cm/min). It was found that the dynamic retention capacity increased 1.4-1.8 times by the zwitterionic polymer grafting in the flow rate range of 1.5-12cm/min. The mechanism of enhanced protein retention on the zwitterionic polymer-grafted surface was proposed. The research proved that zwitterionic polymer modification was promising for the development of new materials for SXC applications.

  17. Nicastrin functions to sterically hinder γ-secretase–substrate interactions driven by substrate transmembrane domain

    PubMed Central

    Bolduc, David M.; Montagna, Daniel R.; Gu, Yongli; Selkoe, Dennis J.; Wolfe, Michael S.

    2016-01-01

    γ-Secretase is an intramembrane-cleaving protease that processes many type-I integral membrane proteins within the lipid bilayer, an event preceded by shedding of most of the substrate’s ectodomain by α- or β-secretases. The mechanism by which γ-secretase selectively recognizes and recruits ectodomain-shed substrates for catalysis remains unclear. In contrast to previous reports that substrate is actively recruited for catalysis when its remaining short ectodomain interacts with the nicastrin component of γ-secretase, we find that substrate ectodomain is entirely dispensable for cleavage. Instead, γ-secretase–substrate binding is driven by an apparent tight-binding interaction derived from substrate transmembrane domain, a mechanism in stark contrast to rhomboid—another family of intramembrane-cleaving proteases. Disruption of the nicastrin fold allows for more efficient cleavage of substrates retaining longer ectodomains, indicating that nicastrin actively excludes larger substrates through steric hindrance, thus serving as a molecular gatekeeper for substrate binding and catalysis. PMID:26699478

  18. An investigation of some sterically hindered amines as potential carbon dioxide scrubbing compounds

    SciTech Connect

    Hook, R.J.

    1997-05-01

    In order to improve the efficiency of the carbon dioxide cycling process and to reduce amine emissions, a series of nonvolatile amino acid salts with sterically hindered amine groups were investigated to determine their potential as direct replacements for monoethanolamine (MEA) in submarine-based CO{sub 2} scrubbers. Absorption from atmospheres containing various levels of CO{sub 2} was measured to assess the total capacities and absorption rates of amine solutions. The regeneration rates and extent of CO{sub 2} desorption were established by heating these solutions. {sup 13}C NMR spectroscopy was used to establish reaction products and solution compositions after both absorption and desorption. Methyl groups substituted adjacent to the amine were found to increase solution absorption capacities but with an overall reduction in absorption rate. Poor absorption rates at low CO{sub 2} levels and precipitation problems would prevent the {alpha}-dimethylamines examined from being used in existing submarine scrubbers. These amines, however, show potential as replacements in industrial CO{sub 2} scrubbing processes.

  19. Relative Stability of Empty Exohedral Fullerenes: π Delocalization versus Strain and Steric Hindrance.

    PubMed

    Wang, Yang; Díaz-Tendero, Sergio; Alcamí, Manuel; Martín, Fernando

    2017-02-01

    Predicting and understanding the relative stability of exohedral fullerenes is an important aspect of fullerene chemistry, since the experimentally formed structures do not generally follow the rules that govern addition reactions or the making of pristine fullerenes. First-principles theoretical calculations are of limited applicability due to the large number of possible isomeric forms, for example, more than 50 billion for C60X8. Here we propose a simple model, exclusively based on topological arguments, that allows one to predict the relative stability of exohedral fullerenes without the need for electronic structure calculations or geometry optimizations. The model incorporates the effects of π delocalization, cage strain, and steric hindrance. We show that the subtle interplay between these three factors is responsible for (i) the formation of non-IPR (isolated pentagon rule) exohedral fullerenes in contrast with their pristine fullerene counterparts, (ii) the appearance of more pentagon-pentagon adjacencies than predicted by the PAPR (pentagon-adjacency penalty rule), (iii) the changes in regioisomer stability due to the chemical nature of the addends, and (iv) the variations in fullerene cage stability with the progressive addition of chemical species.

  20. Antioxidant Properties of 2-Hydroxyethyl Methacrylate-Based Copolymers with Incorporated Sterically Hindered Amine.

    PubMed

    Poláková, L; Raus, V; Kostka, L; Braunová, A; Pilař, J; Lobaz, V; Pánek, J; Sedláková, Z

    2015-09-14

    A series of model linear copolymers of 2-hydroxyethyl methacrylate (HEMA) and a sterically hindered amine derivative [N-(2,2,6,6-tetramethyl-piperidin-4-yl)methacrylamide (HAS)] were synthesized and characterized. Scavenging activities of the copolymers against reactive oxygen species (peroxyl and hydroxyl radicals) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals were determined. It was found that copolymers with medium HAS content (3.5-4.0 mol %) were better scavengers than copolymers with lower and higher HAS content and also than polyHEMA and polyHAS homopolymers and the HAS monomer. Importantly, these copolymers compared favorably even to established low-molecular weight antioxidant standards (BHA and dexpanthenol). Monomer reactivity ratios were determined, and the microstructure of the copolymers was assessed. Subsequently, cross-linked copolymers in the powder and film forms with optimal HAS content were synthesized. Their scavenging activities against the three types of radicals were determined, revealing that these hydrogels are potent scavengers of reactive oxygen species.

  1. Steric hindrance and the enhanced stability of light rare-earth elements in hydrothermal fluids

    USGS Publications Warehouse

    Mayanovic, Robert A.; Anderson, Alan J.; Bassett, William A.; Chou, I.-Ming

    2009-01-01

    A series of X-ray absorption spectroscopy (XAS) experiments were made to determine the structure and stability of aqueous REE (La, Nd, Gd, and Yb) chloride complexes to 500 ??C and 520 MPa. The REE3+ ions exhibit inner-sphere chloroaqua complexation with a steady increase of chloride coordination with increasing temperature in the 150 to 500 ??C range. Furthermore, the degree of chloride coordination of REE3+ inner-sphere chloroaqua complexes decreases significantly from light to heavy REE. These results indicate that steric hindrance drives the reduction of chloride coordination of REE3+ inner-sphere chloroaqua complexes from light to heavy REE. This results in greater stability and preferential transport of light REE3+ over heavy REE3+ ions in saline hydrothermal fluids. Accordingly, the preferential mobility of light REE directly influences the relative abundance of REE in rocks and minerals and thus needs to be considered in geochemical modeling of petrogenetic and ore-forming processes affected by chloride-bearing hydrothermal fluids.

  2. Effects of hydration on steric and electric charge-induced interstitial volume exclusion--a model.

    PubMed

    Øien, Alf H; Justad, Sigrid R; Tenstad, Olav; Wiig, Helge

    2013-09-03

    The presence of collagen and charged macromolecules like glycosaminoglycans (GAGs) in the interstitial space limits the space available for plasma proteins and other macromolecules. This phenomenon, known as interstitial exclusion, is of importance for interstitial fluid volume regulation. Physical/mathematical models are presented for calculating the exclusion of electrically charged and neutral macromolecules that equilibrate in the interstitium under various degrees of hydration. Here, a central hypothesis is that the swelling of highly electrically charged GAGs with increased hydration shields parts of the neutral collagen of the interstitial matrix from interacting with electrically charged macromolecules, such that exclusion of charged macromolecules exhibits change due to steric and charge effects. GAGs are also thought to allow relatively small neutral, but also charged macromolecules neutralized by a very high ionic strength, diffuse into the interior of GAGs, whereas larger macromolecules may not. Thus, in the model, relatively small electrically charged macromolecules, such as human serum albumin, and larger neutral macromolecules such as IgG, will have quite similar total volume exclusion properties in the interstitium. Our results are in agreement with ex vivo and in vivo experiments, and suggest that the charge of GAGs or macromolecular drugs may be targeted to increase the tissue uptake of macromolecular therapeutic agents.

  3. A monofunctional trinuclear platinum complex with steric hindrance demonstrates strong cytotoxicity against tumor cells.

    PubMed

    Wu, Shangnong; Wang, Xiaoyong; He, Yafeng; Zhu, Zhenzhu; Zhu, Chengcheng; Guo, Zijian

    2014-10-01

    Polynuclear platinum complexes constitute a special class of hopeful antitumor agents. In this study, a Y-type monofunctional trinuclear platinum complex (MTPC) with 1,3,5-tris(pyridin-2-ylmethoxy)benzene, ammine and chloride as ligands was synthesized and characterized by (1)H NMR and electrospray ionization mass spectrometry (ESI-MS). The DNA binding mode of MTPC was investigated using circular dichroism spectroscopy and gel electrophoresis, and the reactivity of MTPC towards glutathione was studied by (1)H NMR and ESI-MS. The results show that MTPC can affect the conformation of calf-thymus DNA (CT-DNA) significantly and tends to form 1,4-GG rather than 1,2-GG intrastrand crosslinks, which are different from the instance of cisplatin. MTPC reacts with glutathione quite slowly in comparison with cisplatin because of the steric hindrance. The cytotoxicity of MTPC was tested on the human breast cancer cell line MCF-7, the human non-small-cell lung cancer cell line A549, and the human ovarian cancer cell line Skov-3 by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. MTPC is more potent than or comparable to cisplatin. The cellular inhibition mode of MTPC was examined by flow cytometry using MCF-7 cells. MTPC arrests the cell cycle mainly in G2 or M phase, while cisplatin arrests the cell cycle in S phase. Similar to cisplatin, MTPC kills the cells predominantly through an apoptotic pathway.

  4. Steric exclusion and constraint satisfaction in multi-scale coarse-grained simulations.

    PubMed

    Taylor, William R

    2016-10-01

    An algorithm is described for the interaction of a hierarchy of objects that seeks to circumvent a fundamental problem in coarse-grained modelling which is the loss of fine detail when components become bundled together. A "currants-in-jelly" model is developed that provides a flexible approach in which the contribution of the soft high-level objects (jelly-like) are employed to protect the underlying atomic structure (currants), while still allowing them to interact. Idealised chains were used to establish the parameters to achieve this degree of interaction over a hierarchy spanning four levels and in a more realistic example, the distortion experienced by a protein domain structure during collision was measured and the parameters refined. This model of steric repulsion was then combined with sets of predicted distance constraints, derived from correlated mutation analysis. Firstly, an integral trans-membrane protein was modelled in which the packing of the seven helices was refined but without topological rearrangement. Secondly, an RNA structure was 'folded' under the predicted constraints, starting only from its 2-dimensional secondary structure prediction.

  5. Steric engineering of metal-halide perovskites with tunable optical band gaps.

    PubMed

    Filip, Marina R; Eperon, Giles E; Snaith, Henry J; Giustino, Feliciano

    2014-12-15

    Owing to their high energy-conversion efficiency and inexpensive fabrication routes, solar cells based on metal-organic halide perovskites have rapidly gained prominence as a disruptive technology. An attractive feature of perovskite absorbers is the possibility of tailoring their properties by changing the elemental composition through the chemical precursors. In this context, rational in silico design represents a powerful tool for mapping the vast materials landscape and accelerating discovery. Here we show that the optical band gap of metal-halide perovskites, a key design parameter for solar cells, strongly correlates with a simple structural feature, the largest metal-halide-metal bond angle. Using this descriptor we suggest continuous tunability of the optical gap from the mid-infrared to the visible. Precise band gap engineering is achieved by controlling the bond angles through the steric size of the molecular cation. On the basis of these design principles we predict novel low-gap perovskites for optimum photovoltaic efficiency, and we demonstrate the concept of band gap modulation by synthesising and characterising novel mixed-cation perovskites.

  6. Pluronic® coated sterically stabilized magnetite nanoparticles for hyperthermia applications

    NASA Astrophysics Data System (ADS)

    Rodrigues, E. C.; Morales, M. A.; de Medeiros, S. N.; Suguihiro, N. M.; Baggio-Saitovitch, E. M.

    2016-10-01

    We report the synthesis of magnetite nanoparticles by ball milling of α-Fe in water and its functionalization with oleic acid and Pluronic® F127 for use in hyperthermia applications. The samples were characterized by transmission electron microscopy, DC magnetometry, X-ray diffraction, infrared spectroscopy and heat release studies under an AC magnetic field. The magnetite phase corresponded to 96 wt% and there was a small contribution of 4 wt% of α-Fe. The magnetite particles have a main size of 22 nm and oleic acid layer thickness of 1.9 nm. Magnetic measurements indicate the particles are blocked at 300 K and exhibit the Verwey transition at 119 K. At 5 K the saturation magnetization obtained from the law of approach to saturation was of 95 emu/g. In the heat release studies, the sterically stabilized particles have a temperature increase, ΔT, of 43 °C in 350 s. The Pluronic® coated particles, dispersed in water at 50 mg/ml, exhibited a ΔT=10.5 °C in 350 s, and this value remained nearly constant for periods of up to 650 s. The specific absorption rate (SAR) was of 6.4 W/g indicating that this sample may be used for the lyse of tumor cells.

  7. On the role of steric clashes in methylation control of restriction endonuclease activity

    PubMed Central

    Mierzejewska, Karolina; Bochtler, Matthias; Czapinska, Honorata

    2016-01-01

    Restriction-modification systems digest non-methylated invading DNA, while protecting host DNA against the endonuclease activity by methylation. It is widely believed that the methylated DNA would not ‘fit’ into the binding site of the endonuclease in the productive orientation, and thus steric clashes should account for most of the protection. We test this concept statistically by grafting methyl groups in silico onto non-methylated DNA in co-crystal structures with restriction endonucleases. Clash scores are significantly higher for protective than non-protective methylation (P < 0.05% according to the Wilcoxon rank sum test). Structural data alone are sufficient to distinguish between protective and non-protective DNA methylation with 90% confidence and decision thresholds of 1.1 Å and 48 Å3 for the most severe distance-based and cumulative volume-based clash with the protein, respectively (0.1 Å was deducted from each interatomic distance to allow for coordinate errors). The most severe clashes are more pronounced for protective methyl groups attached to the nitrogen atoms (N6-methyladenines and N4-methylcytosines) than for C5-methyl groups on cytosines. Cumulative clashes are comparable for all three types of protective methylation. PMID:26635397

  8. Overcoming social segregation in health care in Latin America.

    PubMed

    Cotlear, Daniel; Gómez-Dantés, Octavio; Knaul, Felicia; Atun, Rifat; Barreto, Ivana C H C; Cetrángolo, Oscar; Cueto, Marcos; Francke, Pedro; Frenz, Patricia; Guerrero, Ramiro; Lozano, Rafael; Marten, Robert; Sáenz, Rocío

    2015-03-28

    Latin America continues to segregate different social groups into separate health-system segments, including two separate public sector blocks: a well resourced social security for salaried workers and their families and a Ministry of Health serving poor and vulnerable people with low standards of quality and needing a frequently impoverishing payment at point of service. This segregation shows Latin America's longstanding economic and social inequality, cemented by an economic framework that predicted that economic growth would lead to rapid formalisation of the economy. Today, the institutional setup that organises the social segregation in health care is perceived, despite improved life expectancy and other advances, as a barrier to fulfilling the right to health, embodied in the legislation of many Latin American countries. This Series paper outlines four phases in the history of Latin American countries that explain the roots of segmentation in health care and describe three paths taken by countries seeking to overcome it: unification of the funds used to finance both social security and Ministry of Health services (one public payer); free choice of provider or insurer; and expansion of services to poor people and the non-salaried population by making explicit the health-care benefits to which all citizens are entitled.

  9. Barriers, Successes and Enabling Practices of Education for Sustainability in Far North Queensland Schools: A Case Study

    ERIC Educational Resources Information Center

    Evans, Neus; Whitehouse, Hilary; Gooch, Margaret

    2012-01-01

    There are many documented barriers to implementing school-based sustainability. This article examines a) the barriers faced by principals and staff in two regional primary schools in Far North Queensland, Australia, well known for their exemplary practice, and b) ways the barriers were overcome. Through interviews conducted with principals and key…

  10. Disease management in Canada: surmounting barriers to adoption.

    PubMed

    Gallant, Christopher R; MacKinnon, Neil J; Sprague, Denise A

    2007-01-01

    Disease Management (DM) programs are used to optimize economic outcomes and improve patient outcomes. Despite this, relative to the United States, Canadian health care organizations have been slow to adopt them. The objective of this article is to examine the concept of DM programs, the existing evidence to support their use and the barriers to their adoption in Canada. Several solutions aimed at overcoming the barriers to DM in Canada are proposed.

  11. Barriers to Industrial Energy Efficiency - Study (Appendix A), June 2015

    SciTech Connect

    2015-06-01

    This study examines barriers that impede the adoption of energy efficient technologies and practices in the industrial sector, and identifies successful examples and opportunities to overcome these barriers. Three groups of energy efficiency technologies and measures were examined: industrial end-use energy efficiency, industrial demand response, and industrial combined heat and power. This study also includes the estimated economic benefits from hypothetical Federal energy efficiency matching grants, as directed by the Act.

  12. Barriers to Industrial Energy Efficiency - Report to Congress, June 2015

    SciTech Connect

    2015-06-01

    This report examines barriers that impede the adoption of energy efficient technologies and practices in the industrial sector, and identifies successful examples and opportunities to overcome these barriers. Three groups of energy efficiency technologies and measures were examined: industrial end-use energy efficiency, industrial demand response, and industrial combined heat and power. This report also includes the estimated economic benefits from hypothetical Federal energy efficiency matching grants, as directed by the Act.

  13. Systems approach-based mitigation of postharvest diseases to overcome trade barriers for Washington apples

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Speck rot caused by Phacidiopycnis washingtonensis and Sphaeropsis rot caused by S. pyriputrescens were reported as new postharvest fruit rot diseases in Washington State in the mid-2000s. Both diseases can cause significant postharvest losses of fruit if left uncontrolled, and the two fungi have be...

  14. Overcoming the Barriers to Uptake: A Study of 6 Danish Health-Based Serious Games Projects

    ERIC Educational Resources Information Center

    Brown, Damian

    2013-01-01

    Serious gaming for health benefits is moving out of the realm of being potentially interesting, and the authors are starting to see a growing maturity in the field. This study of six serious gaming projects based either wholly or partly in Denmark investigates the changes taking place in the healthcare area based on experiences with serious gaming…

  15. Hematopoiesis from human embryonic stem cells: overcoming the immune barrier in stem cell therapies.

    PubMed

    Priddle, Helen; Jones, D Rhodri E; Burridge, Paul W; Patient, Roger

    2006-04-01

    The multipotency and proliferative capacity of human embryonic stem cells (hESCs) make them a promising source of stem cells for transplant therapies and of vital importance given the shortage in organ donation. Recent studies suggest some immune privilege associated with hESC-derived tissues. However, the adaptability of the immune system makes it unlikely that fully differentiated tissues will permanently evade immune rejection. One promising solution is to induce a state of immune tolerance to a hESC line using tolerogenic hematopoietic cells derived from it. This could provide acceptance of other differentiated tissues from the same line. However, this approach will require efficient multilineage hematopoiesis from hESCs. This review proposes that more efficient differentiation of hESCs to the tolerogenic cell types required is most likely to occur through applying knowledge gained of the ontogeny of complex regulatory signals used by the embryo for definitive hematopoietic development in vivo. Stepwise formation of mesoderm, induction of definitive hematopoietic stem cells, and the application of factors key to their self-renewal may improve in vitro production both quantitatively and qualitatively.

  16. Overcoming perceptions of financial barriers to rotavirus vaccine introduction in Asia.

    PubMed

    Nelson, E Anthony S; de Quadros, Ciro A; Santosham, Mathuram; Parashar, Umesh D; Steele, Duncan

    2013-11-01

    Despite a WHO recommendation in 2009, reaffirmed in 2013, that all countries should consider introducing rotavirus vaccines into their National Immunization Programs, as of June 2013 only 45 have done so. One major consideration appears to have been the costs of the vaccine to countries. Of concern, is that Asian countries have been slow to introduce rotavirus vaccines despite having robust data that could inform the decision-making process. Although decisions on new vaccine introduction are very complex and vary by country and region, economic evaluations are often pivotal once vaccine efficacy and safety has been established, and disease burden documented and communicated. Unfortunately, with private sector list prices of vaccines often used in economic evaluations, rather than a potential public health sector pricing structure, policy-makers may defer decisions on rotavirus vaccine introduction based on the belief that "the vaccine price is too high," even though this might be based on erroneous data. The Pan American Health Organization's Revolving Fund provides one example of how vaccine price can be made more competitive and transparent through a regional tendering process. Other mechanisms, such as tiered pricing and UNICEF procurement, also exist that could help Asian and other countries move forward more quickly with rotavirus vaccine introduction.

  17. Overcoming Barriers to the Remediation of Carbon Tetrachloride Through Manipulation of Competing Reaction Mechanisms

    SciTech Connect

    Tratnyek, Paul G.; Amonette, James E.; Bylaska, Eric J.

    2004-03-29

    Most approaches that have been proposed for the remediation of groundwater contaminated with carbon tetrachloride produce chloroform as the major product and methylene chloride as a minor product. Both of these products are nearly as persistent and problematic as the parent compound, but competing reaction pathways produce the more desirable products carbon monoxide and/or formate. Branching between these reaction pathways is highly variable, but the controlling factors have not been identified. To improve the applicability of reductive remediation technologies to the large plumes of carbon tetrachloride at several DOE sites, we are pursuing the complete characterization of the mechanisms and kinetics of competing degradation reactions of carbon tetrachloride through laboratory experiments closely coordinated with theoretical modeling studies. The results are beginning to suggest strategies for maximizing the yield of desirable products from carbon tetrachloride degradation, which will be tested in column model systems using real site waters and matrix materials.

  18. Mobile "Comfort" Zones: Overcoming Barriers to Enable Facilitated Learning in the Workplace

    ERIC Educational Resources Information Center

    Holley, Debbie; Sentance, Sue

    2015-01-01

    The affordances of mobile technologies are well documented (Vavoula (2004); Wali (2008); Pachler et al (2010); Cook (2011); Sharples (2013). Linked with the rapid expansion of the "SMART" phones, where users access fast/high quality information, new opportunities are offered to engage students at a time/place of their own choosing. Our…

  19. Overcoming the organization-practice barrier in sports injury prevention: A nonhierarchical organizational model.

    PubMed

    Dahlström, Ö; Jacobsson, J; Timpka, T

    2015-08-01

    The organization of sports at the national level has seldom been included in scientific discussions of sports injury prevention. The aim of this study was to develop a model for organization of sports that supports prevention of overuse injuries. The quality function deployment technique was applied in seminars over a two-season period to develop a national organizational structure for athletics in Sweden that facilitates prevention of overuse injuries. Three central features of the resulting model for organization of sports at the national level are (a) diminishment of the organizational hierarchy: participatory safety policy design is introduced through annual meetings where actors from different sectors of the sporting community discuss training, injury prevention, and sports safety policy; (b) introduction of a safety surveillance system: a ubiquitous system for routine collection of injury and illness data; and (c) an open forum for discussion of safety issues: maintenance of a safety forum for participants from different sectors of the sport. A nonhierarchical model for organization of sports at the national level - facilitated by modern information technology - adapted for the prevention of overuse injuries has been developed. Further research is warranted to evaluate the new organizational model in prospective effectiveness studies.

  20. Overcoming Barriers in Oncolytic Virotherapy with HDAC Inhibitors and Immune Checkpoint Blockade.

    PubMed

    Marchini, Antonio; Scott, Eleanor M; Rommelaere, Jean

    2016-01-06

    Oncolytic viruses (OVs) target and destroy cancer cells while sparing their normal counterparts. These viruses have been evaluated in numerous studies at both pre-clinical and clinical levels and the recent Food and Drug Administration (FDA) approval of an oncolytic herpesvirus-based treatment raises optimism that OVs will become a therapeutic option for cancer patients. However, to improve clinical outcome, there is a need to increase OV efficacy. In addition to killing cancer cells directly through lysis, OVs can stimulate the induction of anti-tumour immune responses. The host immune system thus represents a "double-edged sword" for oncolytic virotherapy: on the one hand, a robust anti-viral response will limit OV replication and spread; on the other hand, the immune-mediated component of OV therapy may be its most important anti-cancer mechanism. Although the relative contribution of direct viral oncolysis and indirect, immune-mediated oncosuppression to overall OV efficacy is unclear, it is likely that an initial period of vigorous OV multiplication and lytic activity will most optimally set the stage for subsequent adaptive anti-tumour immunity. In this review, we consider the use of histone deacetylase (HDAC) inhibitors as a means of boosting virus replication and lessening the negative impact of innate immunity on the direct oncolytic effect. We also discuss an alternative approach, aimed at potentiating OV-elicited anti-tumour immunity through the blockade of immune checkpoints. We conclude by proposing a two-phase combinatorial strategy in which initial OV replication and spread is maximised through transient HDAC inhibition, with anti-tumour immune responses subsequently enhanced by immune checkpoint blockade.

  1. Setting Learning Analytics in Context: Overcoming the Barriers to Large-Scale Adoption

    ERIC Educational Resources Information Center

    Ferguson, Rebecca; Macfadyen, Leah P.; Clow, Doug; Tynan, Belinda; Alexander, Shirley; Dawson, Shane

    2014-01-01

    A core goal for most learning analytic projects is to move from small-scale research towards broader institutional implementation, but this introduces a new set of challenges because institutions are stable systems, resistant to change. To avoid failure and maximize success, implementation of learning analytics at scale requires explicit and…

  2. Videos Bridging Asia and Africa: Overcoming Cultural and Institutional Barriers in Technology-Mediated Rural Learning

    ERIC Educational Resources Information Center

    Van Mele, Paul; Wanvoeke, Jonas; Akakpo, Cyriaque; Dacko, Rosaline Maiga; Ceesay, Mustapha; Beavogui, Louis; Soumah, Malick; Anyang, Robert

    2010-01-01

    Will African farmers watch and learn from videos featuring farmers in Bangladesh? Learning videos on rice seed management were made with rural women in Bangladesh. By using a new approach, called zooming-in, zooming-out, the videos were of regional relevance and locally appropriate. When the Africa Rice Center (AfricaRice) introduced them to…

  3. Women Community College Presidents: A Qualitative Approach to Exploring Leadership and Overcoming Potential Barriers

    ERIC Educational Resources Information Center

    O'Roark, Jordan J.

    2015-01-01

    Since the establishment of American higher education, the presidential profile for institutions has lacked the gender diversity in presidential leadership positions. Though women have taken positive strides as senior executive officers in higher education in the past quarter-century, the conventional post-secondary president is a white, married…

  4. Overcoming perceptions of financial barriers to rotavirus vaccine introduction in Asia

    PubMed Central

    Nelson, E Anthony S; de Quadros, Ciro A; Santosham, Mathuram; Parashar, Umesh D; Steele, A Duncan

    2013-01-01

    Despite a WHO recommendation in 2009, reaffirmed in 2013, that all countries should consider introducing rotavirus vaccines into their National Immunization Programs, as of June 2013 only 45 have done so. One major consideration appears to have been the costs of the vaccine to countries. Of concern, is that Asian countries have been slow to introduce rotavirus vaccines despite having robust data that could inform the decision-making process. Although decisions on new vaccine introduction are very complex and vary by country and region, economic evaluations are often pivotal once vaccine efficacy and safety has been established, and disease burden documented and communicated. Unfortunately, with private sector list prices of vaccines often used in economic evaluations, rather than a potential public health sector pricing structure, policy-makers may defer decisions on rotavirus vaccine introduction based on the belief that “the vaccine price is too high,” even though this might be based on erroneous data. The Pan American Health Organization’s Revolving Fund provides one example of how vaccine price can be made more competitive and transparent through a regional tendering process. Other mechanisms, such as tiered pricing and UNICEF procurement, also exist that could help Asian and other countries move forward more quickly with rotavirus vaccine introduction. PMID:23955246

  5. Overcoming the stromal barrier for targeted delivery of HPMA copolymers to pancreatic tumors.

    PubMed

    Buckway, Brandon; Wang, Yongjian; Ray, Abhijit; Ghandehari, Hamidreza

    2013-11-01

    Delivery of macromolecules to pancreatic cancer is inhibited by a dense extracellular matrix composed of hyaluronic acid, smooth muscle actin and collagen fibers. Hyaluronic acid causes a high intratumoral fluidic pressure which prevents diffusion and penetration into the pancreatic tumor. This study involves the breaking down of hyaluronic acid by treating CAPAN-1 xenograft tumors in athymic nu/nu mice with targeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers radiolabeled with (111)In for single photon emission computerized tomography (SPECT) imaging. Two targeting strategies were investigated including αvβ3 integrin and HER2 receptors. HPMA copolymers were targeted to these receptors by conjugating short peptide ligands cRGDfK and KCCYSL to the side chains of the copolymer. Results demonstrate that tumor targeting can be achieved in vivo after treatment with hyaluronidase. This approach shows promise for enhanced delivery of polymer-peptide conjugates to solid tumors.

  6. Overcoming Barriers in Oncolytic Virotherapy with HDAC Inhibitors and Immune Checkpoint Blockade

    PubMed Central

    Marchini, Antonio; Scott, Eleanor M.; Rommelaere, Jean

    2016-01-01

    Oncolytic viruses (OVs) target and destroy cancer cells while sparing their normal counterparts. These viruses have been evaluated in numerous studies at both pre-clinical and clinical levels and the recent Food and Drug Administration (FDA) approval of an oncolytic herpesvirus-based treatment raises optimism that OVs will become a therapeutic option for cancer patients. However, to improve clinical outcome, there is a need to increase OV efficacy. In addition to killing cancer cells directly through lysis, OVs can stimulate the induction of anti-tumour immune responses. The host immune system thus represents a “double-edged sword” for oncolytic virotherapy: on the one hand, a robust anti-viral response will limit OV replication and spread; on the other hand, the immune-mediated component of OV therapy may be its most important anti-cancer mechanism. Although the relative contribution of direct viral oncolysis and indirect, immune-mediated oncosuppression to overall OV efficacy is unclear, it is likely that an initial period of vigorous OV multiplication and lytic activity will most optimally set the stage for subsequent adaptive anti-tumour immunity. In this review, we consider the use of histone deacetylase (HDAC) inhibitors as a means of boosting virus replication and lessening the negative impact of innate immunity on the direct oncolytic effect. We also discuss an alternative approach, aimed at potentiating OV-elicited anti-tumour immunity through the blockade of immune checkpoints. We conclude by proposing a two-phase combinatorial strategy in which initial OV replication and spread is maximised through transient HDAC inhibition, with anti-tumour immune responses subsequently enhanced by immune checkpoint blockade. PMID:26751469

  7. Using synthetic biology to distinguish and overcome regulatory and functional barriers related to nitrogen fixation.

    PubMed

    Wang, Xia; Yang, Jian-Guo; Chen, Li; Wang, Ji-Long; Cheng, Qi; Dixon, Ray; Wang, Yi-Ping

    2013-01-01

    Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ~100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase-LacI expression system was used to replace the σ(54)-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ~42% of the nitrogenase activity of the σ(54)-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology.

  8. Overcoming Barriers to Educational Analytics: How Systems Thinking and Pragmatism Can Help

    ERIC Educational Resources Information Center

    Macfadyen, Leah P.

    2017-01-01

    Learning technologies are now commonplace in education, and generate large volumes of educational data. Scholars have argued that analytics can and should be employed to optimize learning and learning environments. This article explores what is really meant by "analytics", describes the current best-known examples of institutional…

  9. Overcoming Language Barriers in Health Care: Costs and Benefits of Interpreter Services

    PubMed Central

    Jacobs, Elizabeth A.; Shepard, Donald S.; Suaya, Jose A.; Stone, Esta-Lee

    2004-01-01

    Objectives. We assessed the impact of interpreter services on the cost and the utilization of health care services among patients with limited English proficiency. Methods. We measured the change in delivery and cost of care provided to patients enrolled in a health maintenance organization before and after interpreter services were implemented. Results. Compared with English-speaking patients, patients who used the interpreter services received significantly more recommended preventive services, made more office visits, and had more prescriptions written and filled. The estimated cost of providing interpreter services was $279 per person per year. Conclusions. Providing interpreter services is a financially viable method for enhancing delivery of health care to patients with limited English proficiency. PMID:15117713

  10. Evolving from academic to academic entrepreneur: overcoming barriers to scientific progress and finance.

    PubMed

    Miller, Andrew D

    2016-07-01

    The overall goal of my career as an academic chemist has always been the design and creation of advanced therapeutics and diagnostics that address unmet medical need in the management of chronic diseases. Realising this goal has been an immensely difficult process involving multidisciplinary problem-driven research at the chemistry-biology-medicine interfaces. With success in the laboratory, I started seriously to question the value of remaining an academic whose career is spent in the pursuit of knowledge and understanding alone without making any significant effort to translate knowledge and understanding gained into products of genuine utility for public benefit. Therefore, I elected by choice to become an academic entrepreneur, seeking opportunities wherever possible for the translation of the best of my personal and collaborative academic research work into potentially valuable and useful products. This choice has brought with it many unexpected difficulties and challenges. Nevertheless, progress bas been made and sufficient learnt to suggest that this would be an appropriate moment to take stock and provide some personal reflections on what it takes to design and create advanced therapeutics and diagnostics in the laboratory then seek to develop, innovate and translate the best towards market.

  11. Colonisation in social species: the importance of breeding experience for dispersal in overcoming information barriers

    PubMed Central

    Payo-Payo, A.; Genovart, M.; Sanz-Aguilar, A.; Greño, J. L.; García-Tarrasón, M.; Bertolero, A.; Piccardo, J.; Oro, D.

    2017-01-01

    Studying colonisation is crucial to understand metapopulations, evolutionary ecology and species resilience to global change. Unfortunately, few empirical data are available because field monitoring that includes empty patches at large spatiotemporal scales is required. We examine the colonisation dynamics of a long-lived seabird over 34 years in the western Mediterranean by comparing population and individual data from both source colony and the newly-formed colonies. Since social information is not available, we hypothesize that colonisation should follow particular dispersal dynamics and personal information must be crucial in decision making. We test if adverse breeding conditions trigger colonisation events, if personal information plays a role in colonisation and if colonisers experience greater fitness. Our results show a temporal mismatch between colonisation events and both density-dependence and perturbations at the source colony, probably because colonisers needed a longer prospecting period to compensate for the lack of public information. Colonisers were mostly experienced individuals gaining higher breeding success in the new colony. Our results highlight the demographic value that experienced individuals can have on metapopulation dynamics of social long-lived organisms. PMID:28211483

  12. Primary health care in developing countries: overcoming operational, technical, and social barriers.

    PubMed

    Chen, L C

    1986-11-29

    An analysis of survey data from Matlab, Bangladesh, suggests that the provision of primary health care is a more complex process than is reflected by current strategies. The Bangladesh experience indicates that single-outcome indicators (e.g., deaths averted) for assessing the effect of health measures, while necessary for comparing the cost-effectiveness of various approaches, rarely encapsulate all the aims of an intervention. For example, in the year after the introduction in Matlab of modern contraception and tetanus immunization for pregnant women, the intervention population had ab0ut a 25% lower crude birth and death rate, yet little difference was observed in infant mortality rates. Policies aimed at contering single diseases may cause factors such as nutrition, which has important biosocial interactions with infection, to be undervalued. Rather than viewing childhood morality in relation to specific diseases--an approach that promotes an emphsis on tchnology--childhood mortality should be seen as the result of sequential insults accumulated over time. the reluctance of eligible women to accept tetanus vaccine and the greater utilization of diarrhea treatment services for male than female children are examples of the significance of the demand factor. Also needed is improved knowledge of the interaction between the structure of health care delivery systems and a population's political economy. Public investments for primary health care in India have been targeted to large-scale public systems operated by a bureaucracy biased toward procedure rather than performance. Finally, future research should incorporate the strengths of both the natural and the social sciencs.

  13. Overcoming Barriers: Tailoring Climate Education for Latino and non-Latino Citizen to Impact Decision Making

    NASA Astrophysics Data System (ADS)

    Estrada, M.; Boudrias, M. A.; Silva-Send, N. J.; Gershunov, A.; Anders, S.

    2013-12-01

    Culture has been shown to be an important determinant of Latino/Hispanic American environmental attitudes (Schultz, Unipan, & Gamba, 2000), which might help to explain the underrepresentation of Latinos in the U.S. 'environmental' movement. With shifting U.S. demographics, however, there is increased urgency to understand how Latinos integrate into the community that is concerned and literate about climate change. As part of the Climate Education Partners (CEP) work in San Diego, we investigated how to address this ethnic group disparity. In this paper, we describe a study of how climate change science knowledge relates to Latino and Non-Latino citizen (a) engagement in conservation behaviors and (b) more informed decision-making. Drawing upon previous work on the Tripartite Integration Model of Social Influence (TIMSI) (Estrada et al., 2011), we hypothesized that climate change knowledge that promotes efficacy (i.e., a sense that one can do something) would relate to greater engagement in conservation behaviors and more informed decision-making (both common of community members concerned about climate change). To test this model, 1001 San Diego residence participated in a telephone survey in which the attitudes towards climate change were assessed using '6 Americas' segmentation (Leiserowitz et al., 2011), in addition to climate change science knowledge, efficacy, values, and engagement in weekly and yearly climate change friendly behaviors (e.g., conservation, transportation, community engagement behaviors). Results showed that there were significant differences in the 6 America segmentation distributions, knowledge, efficacy and behavioral engagement with Latinos significantly more concerned than Non-Latinos, and reporting greater knowledge, efficacy and engagement in behaviors. However, data from both groups showed support for the TIMSI theoretical framework, such that efficacy mediated the relationship between climate change knowledge and behavior. Thus, for both groups, climate change science knowledge was more likely to result in behavioral engagement when the science knowledge was accompanied with the belief that one has the ability to engage in behaviors that mitigate or adapt to climate change (i.e., efficacy). Implications for how to improve both Latino and Non-Latino climate change education that results in informed decision-making and greater integration into the community concerned about climate change will be discussed.

  14. Using Synthetic Biology to Distinguish and Overcome Regulatory and Functional Barriers Related to Nitrogen Fixation

    PubMed Central

    Wang, Xia; Yang, Jian-Guo; Chen, Li; Wang, Ji-Long; Cheng, Qi; Dixon, Ray; Wang, Yi-Ping

    2013-01-01

    Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ∼100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase–LacI expression system was used to replace the σ54-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ∼42% of the nitrogenase activity of the σ54-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology. PMID:23935879

  15. Can An Academic Health Care System Overcome Barriers to Clinical Guideline Implementation?

    DTIC Science & Technology

    2005-01-01

    Cardiology/ American Heart Association (ACC/AHA) practice guidelines state that the utilization of beta- blockers in patients with known coronary disease or...surgery: a report of the American College of Cardiology/ American Heart Association task force on practice guidelines [American College of Cardiology

  16. Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

    DTIC Science & Technology

    2014-10-01

    Multilevel Intraspinal Stem Cell Therapy for Amyotrophic Lateral Sclerosis (ALS). Congress of Neurological Surgeons Annual Meeting (Boston, October...NM. Preclinical Validation of Multilevel Intraspinal Stem Cell Therapy for Amyotrophic Lateral Sclerosis (ALS). Submitted. Appendix 3...transplant and serially post-transplant. Furthermore, plasma was collected from six patients with Amyotrophic Lateral Sclerosis enrolled in the Phase 1

  17. Older Teens in TANF Families: Overcoming Barriers to Self-Sufficiency.

    ERIC Educational Resources Information Center

    Kaplan, Jan

    2001-01-01

    Older teens living in families receiving Temporary Assistance to Needy Families (TANF) face serious sociodemographic disadvantages. When combined with the characteristic risk-taking behaviors of adolescence, these disadvantages pose a threat to TANF teens' immediate and future physical, psychological, and emotional health and to their long-term…

  18. Understanding and overcoming barriers to timely discharge from the pediatric units

    PubMed Central

    Mustafa, Amira; Mahgoub, Samar

    2016-01-01

    Delays in the discharge of hospital patients cause a backlog for new admissions from the Emergency Departments (ED), outpatient clinics, and transfers from the Intensive Care Units (ICU). A variety of initiatives have been reported on previously which aim to tackle this problem with variable success. In this quality improvement project, we aimed to increase the proportion of discharged patients who leave the paediatric unit by 12:00 Noon from 7% to 30% by May 2015. A baseline discharge process map was studied to understand the possible causes of the delays. A survey was conducted to look for the most likely cause for the delay. A data collection tool was designed to record the various steps in the discharge process for the pre-and post-intervention phases. Using a series of PDSA cycles, interventions were introduced. The average time for the discharge process was two hours and the baseline average percent of patients discharged by 12:00 Noon was 7% of all discharges. The leading cause for the delayed discharges was late orders by the physicians. Post-intervention, there was increase in the percentage of patients discharged by 12:00 Noon from 7% to 34%. 42% of discharged patients had appropriate reasons for afternoon discharge. By excluding these patients, the percentage of adjusted timely morning discharge has increased from 36% to 70%. Continuous monitoring and engagement of teams with regular feedback were the most important factors in achieving and sustaining improvement in the timely morning discharge of patients from our paediatric units. PMID:27752313

  19. Overcoming the nail barrier: A systematic investigation of ungual chemical penetration enhancement.

    PubMed

    Brown, M B; Khengar, R H; Turner, R B; Forbes, B; Traynor, M J; Evans, C R G; Jones, S A

    2009-03-31

    This study investigated the in vitro nail permeability of penetrants of varying lipophilicity-caffeine (CF, logP -0.07), methylparaben (MP, logP 1.96) and terbinafine (TBF, logP 3.3) and the effect of 2 novel penetration enhancers (PEs), thioglycolic acid (TA) and urea hydrogen peroxide (urea H(2)O(2)) on their permeation. Studies were conducted using full thickness human nail clippings and ChubTur((R)) diffusion cells and penetrants were applied as saturated solutions. The rank order of steady-state penetrant flux through nails without PE application (MP>CF>TBF) suggested a greater sensitivity to penetrant molecular weight rather than logP. TA increased the flux of CF and MP approximately 4- and approximately 2-fold, respectively, whilst urea H(2)O(2) proved ineffective at enhancing permeability. The sequential application of TA followed by urea H(2)O(2) increased TBF and CF flux ( approximately 19- and approximately 4-fold, respectively) but reversing the application order of the PEs was only mildly effective at increasing just MP flux ( approximately 2-fold). Both nail PEs are likely to function via disruption of keratin disulphide bonds and the associated formation of pores that provide more 'open' drug transport channels. Effects of the PEs were penetrant specific, but the use of a reducing agent (TA) followed by an oxidising agent (urea H(2)O(2)) dramatically improved human nail penetration.

  20. Overcoming Medicaid Reimbursement Barriers to Funding School Nursing Services for Low-Income Children with Asthma

    ERIC Educational Resources Information Center

    Malcarney, Mary-Beth; Horton, Katherine; Seiler, Naomi

    2016-01-01

    Background: School nurses can provide direct services for children with asthma, educate, and reinforce treatment recommendations to children and their families, and coordinate the school-wide response to students' asthma emergencies. Unfortunately, school-based health services today depend on an unreliable patchwork of funding. Limited state and…

  1. Overcoming Barriers to Improve Breastfeeding Self-Efficacy in Older Adolescent Mothers

    ERIC Educational Resources Information Center

    Beattie-Fairchild, Cindy

    2013-01-01

    A lack of breastfeeding has negative consequences on mother and infant by creating health disparities with a higher incidence of morbidity and mortality. Nationwide, fewer than 60% of mothers younger than age 20 years breastfed exclusively, while fewer than 20% did so in the community being studied. The purpose of this qualitative case study was…

  2. Education for All Aspects of the Industry: Overcoming Barriers to Broad-Based Training.

    ERIC Educational Resources Information Center

    Bailey, Thomas; And Others

    This report is designed to help the educational community develop the "all aspects of the industry" (AAI) strategy promoted in the Perkins Vocational Education Act. The introduction describes the current status of AAI and elaborates on three arguments for it: (1) AAI is a pedagogic strategy that promotes more effective learning; (2) better…

  3. Colonisation in social species: the importance of breeding experience for dispersal in overcoming information barriers

    NASA Astrophysics Data System (ADS)

    Payo-Payo, A.; Genovart, M.; Sanz-Aguilar, A.; Greño, J. L.; García-Tarrasón, M.; Bertolero, A.; Piccardo, J.; Oro, D.

    2017-02-01

    Studying colonisation is crucial to understand metapopulations, evolutionary ecology and species resilience to global change. Unfortunately, few empirical data are available because field monitoring that includes empty patches at large spatiotemporal scales is required. We examine the colonisation dynamics of a long-lived seabird over 34 years in the western Mediterranean by comparing population and individual data from both source colony and the newly-formed colonies. Since social information is not available, we hypothesize that colonisation should follow particular dispersal dynamics and personal information must be crucial in decision making. We test if adverse breeding conditions trigger colonisation events, if personal information plays a role in colonisation and if colonisers experience greater fitness. Our results show a temporal mismatch between colonisation events and both density-dependence and perturbations at the source colony, probably because colonisers needed a longer prospecting period to compensate for the lack of public information. Colonisers were mostly experienced individuals gaining higher breeding success in the new colony. Our results highlight the demographic value that experienced individuals can have on metapopulation dynamics of social long-lived organisms.

  4. Overcoming the Barriers of Civil/Military Industrial Integration and of Buying Commercial Goods and Services

    DTIC Science & Technology

    2015-05-13

    Chair Director, Center for Public Policy and Private Enterprise School of Public Policy University of Maryland Naval Postgraduate School 12th...University of Maryland,School of Public Policy/Center for Public Policy and Private Enterprise,2101 Van Munching Hall ,College Park,MD,20742 8...Property • Extensive Oversight and auditing • 50% Depot law (on maintenance and “core” work) • Legislative Elimination of Public / Private competitions

  5. Identifying and Overcoming Barriers to Diabetes Management in the Elderly: An Intervention Study

    DTIC Science & Technology

    2011-06-01

    inadequate previous education -low health literacy Presence of co-morbidities interfering with self-care -cognitive dysfunction -depression...suggesting overall problems with adherence, and were having trouble reading food labels (p=0.05) suggesting possible problems with health literacy . Higher

  6. Identifying and Overcoming Barriers to Diabetes Management in the Elderly: An Intervention Study

    DTIC Science & Technology

    2009-06-01

    food labels (p=0.05), suggesting possible problems with health literacy . Higher frequency of falls, fear of falls, and difficulty walking were more...problems with health literacy . Higher frequency of falls, fear of falls, and difficulty walking were more common in the group having problems taking

  7. Overcoming Barriers in the Use of Adaptive and Assistive Technology in Special Education.

    ERIC Educational Resources Information Center

    Bushrow, Kathy M.; Turner, Keith D.

    This paper examines change and change facilitators as they affect full use of adaptive and assistive technology (AAT) in special education, and compares qualitative versus quantitative methods of researching the change process. Four administrators and two teachers from a rural school district completed the Stages of Concern Questionnaire, which…

  8. Overcoming Unintentional Barriers with Intentional Strategies: Educating Faculty about Student Disabilities

    ERIC Educational Resources Information Center

    Forrest, Krista D.

    2003-01-01

    Krista Forrest is an Assistant Professor in the Department of Psychology at the University of Nebraska at Kearney, where she teaches general psychology and life span development as well as advanced courses in adolescent psychology, group dynamics, and psychology and law. A graduate of North Carolina State University with a MS in developmental…

  9. Workflow technology: the new frontier. How to overcome the barriers and join the future.

    PubMed

    Shefter, Susan M

    2006-01-01

    Hospitals are catching up to the business world in the introduction of technology systems that support professional practice and workflow. The field of case management is highly complex and interrelates with diverse groups in diverse locations. The last few years have seen the introduction of Workflow Technology Tools, which can improve the quality and efficiency of discharge planning by the case manager. Despite the availability of these wonderful new programs, many case managers are hesitant to adopt the new technology and workflow. For a myriad of reasons, a computer-based workflow system can seem like a brick wall. This article discusses, from a practitioner's point of view, how professionals can gain confidence and skill to get around the brick wall and join the future.

  10. Overcoming the Language Barrier. Third European Congress on Information Systems and Networks, Vol. 1.

    ERIC Educational Resources Information Center

    Commission des Communautes Europeennes (Luxembourg).

    The papers presented here have a double objective: to give those responsible for the Action plan for the improvement of information transfer between European languages a good view of existing and developing systems and to make future users of EURONET acquainted with methods and tools that will soon be available. The papers are arranged under six…

  11. Educational Planning for the Gifted. Overcoming Cultural, Geographic and Socioeconomic Barriers

    ERIC Educational Resources Information Center

    Baldwin, Alexinia Y., Ed.; And Others

    The book presents theoretical considerations and practical recommendations concerned with school planning for gifted children who might not be identified nor have an opportunity to develop their mental capacities because of external influences such as cultural diversity, socioeconomic status, or geographic isolation. Six different approaches to…

  12. Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

    DTIC Science & Technology

    2012-10-01

    first utilized oriP/EBNA1 ( Epstein - Barr nuclear antigen-1)-based reprogramming vectors that utilize episomal expression of the 6 pluripotency factors...phenotype observed in during transplantation. Non-integrating methods, such as plasmid-based and Sendai single-stranded RNA viruses , avoid random...reprogramming factors is required in Yucatan minipig cells. Recently, Sendai virus (SeV)-based reprogramming technology has been reported as an

  13. Achieving Cross-Domain Synergy: Overcoming Service Barriers to Joint Force 2020

    DTIC Science & Technology

    2014-06-13

    Davis, Mr. Russ Crumrine, and Mr. Kevin Gentzler for their continued support during this lengthy process . Your prompt feedback and excellent guidance...and guiding me every step of the way. I know that this process has helped me to see the big picture and has developed my understanding of military...Component Commander JOAC Joint Operational Access Concept JOPP Joint Operational Planning Process JOPPA Joint Operational Planning Process Air

  14. Confidence-Based Learning CME: Overcoming Barriers in Irritable Bowel Syndrome with Constipation

    ERIC Educational Resources Information Center

    Cash, Brooks; Mitchner, Natasha A.; Ravyn, Dana

    2011-01-01

    Introduction: Performance of health care professionals depends on both medical knowledge and the certainty with which they possess it. Conventional continuing medical education interventions assess the correctness of learners' responses but do not determine the degree of confidence with which they hold incorrect information. This study describes…

  15. Overcoming language and literacy barriers in safety and health training of agricultural workers.

    PubMed

    Arcury, Thomas A; Estrada, Jorge M; Quandt, Sara A

    2010-07-01

    The workforce in all areas of United States agriculture and forestry is becoming increasingly diverse in language, culture, and education. Many agricultural workers are immigrants who have limited English language skills and limited educational attainment. Providing safety and health training to this large, diverse, dispersed, and often transient population of workers is challenging. This review, prepared for the 2010 Agricultural Safety and Health Council of America/National Institute for Occupational Safety and Health conference, "Be Safe, Be Profitable: Protecting Workers in Agriculture," is divided into five sections. First, we describe the occupational and demographic characteristics of agricultural workers in the United States to highlight their safety and health training needs. Second, we summarize current research on the social and cultural attributes of agricultural workers and agricultural employers that affect the provision of safety and health training. Worker and employer attributes include language, literacy, financial limitations, work beliefs, and health beliefs. Third, we review current initiatives addressing safety and health training for agricultural workers that consider worker language and literacy. These initiatives are limited to a few specific topics (e.g., pesticides, heat stress); they do not provide general programs of safety training that would help establish a culture of workplace safety. However, several innovative approaches to health and safety training are being implemented, including the use of community-based participatory approaches and lay health promoter programs. Fourth, the limited industry response for safety training with this linguistically diverse and educationally limited workforce is summarized. Finally, gaps in knowledge and practice are summarized and recommendations to develop educationally, culturally, and linguistically appropriate safety and health training are presented.

  16. Overcoming Psychosocial Barriers to Maternal Exercise: Intervention Strategies to Improve Participation and Adherence

    ERIC Educational Resources Information Center

    Schoenfeld, Brad; Tiryaki-Sonmez, Gul

    2011-01-01

    Poor adherence to physical activity programmes during pregnancy is a serious national issue, one that has detrimental effects on a large percentage of the population. Not only does a lack of activity result in a decrease in quality of life for women during term, but the effects can carry over well after pregnancy, potentially leading to increased…

  17. Tropism-modified AAV vectors overcome barriers to successful cutaneous therapy.

    PubMed

    Sallach, Jessica; Di Pasquale, Giovanni; Larcher, Fernando; Niehoff, Nadine; Rübsam, Matthias; Huber, Anke; Chiorini, Jay; Almarza, David; Eming, Sabine A; Ulus, Hikmet; Nishimura, Stephen; Hacker, Ulrich T; Hallek, Michael; Niessen, Carien M; Büning, Hildegard

    2014-05-01

    Autologous human keratinocytes (HK) forming sheet grafts are approved as skin substitutes. Genetic engineering of HK represents a promising technique to improve engraftment and survival of transplants. Although efficacious in keratinocyte-directed gene transfer, retro-/lentiviral vectors may raise safety concerns when applied in regenerative medicine. We therefore optimized adeno-associated viral (AAV) vectors of the serotype 2, characterized by an excellent safety profile, but lacking natural tropism for HK, through capsid engineering. Peptides, selected by AAV peptide display, engaged novel receptors that increased cell entry efficiency by up to 2,500-fold. The novel targeting vectors transduced HK with high efficiency and a remarkable specificity even in mixed cultures of HK and feeder cells. Moreover, differentiated keratinocytes in organotypic airlifted three-dimensional cultures were transduced following topical vector application. By exploiting comparative gene analysis we further succeeded in identifying αvβ8 integrin as a target receptor thus solving a major challenge of directed evolution approaches and describing a promising candidate receptor for cutaneous gene therapy.

  18. Overcoming Language and Literacy Barriers in Safety and Health Training of Agricultural Workers

    PubMed Central

    Arcury, Thomas A.; Estrada, Jorge M.; Quandt, Sara A.

    2010-01-01

    The workforce in all areas of United States agriculture and forestry is becoming increasingly diverse in language, culture, and education. Many agricultural workers are immigrants who have limited English language skills and limited educational attainment. Providing safety and health training to this large, diverse, dispersed, and often transient population of workers is challenging. This review, prepared for the 2010 Agricultural Safety and Health Council of America/National Institute for Occupational Safety and Health conference, “Be Safe, Be Profitable: Protecting Workers in Agriculture,” is divided into five sections. First, we describe the occupational and demographic characteristics of agricultural workers in the US to highlight their safety and health training needs. Second, we summarize current research on the social and cultural attributes of agricultural workers and agricultural employers that affect the provision of safety and health training. Worker and employer attributes include language, literacy, financial limitations, work beliefs, and health beliefs. Third, we review current initiatives addressing safety and health training for agricultural workers that consider worker language and literacy. These initiatives are limited to a few specific topics (e.g., pesticides, heat stress); they do not provide general programs of safety training that would help establish a culture of workplace safety. However, several innovative approaches to health and safety training are being implemented, including the use of community-based participatory approaches and lay health promoter programs. Fourth, the limited industry response for safety training with this linguistically diverse and educationally limited workforce is summarized. Finally, gaps in knowledge and practice are summarized and recommendations to develop educationally, culturally, and linguistically appropriate safety and health training are presented. PMID:20665309

  19. Overcoming the Barrier of Low Efficiency during Genetic Transformation of Streptococcus mitis

    PubMed Central

    Salvadori, Gabriela; Junges, Roger; Morrison, Donald A.; Petersen, Fernanda C.

    2016-01-01

    Objective: Streptococcus mitis is a predominant oral colonizer, but difficulties in genetic manipulation of this species have hampered our understanding of the mechanisms it uses for colonization of oral surfaces. The aim of this study was to reveal optimal conditions for natural genetic transformation in S. mitis and illustrate its application in direct genome editing. Methods: Luciferase reporter assays were used to assess gene expression of the alternative sigma factor (σX) in combination with natural transformation experiments to evaluate the efficiency by which S. mitis activates the competence system and incorporates exogenous DNA. Optimal amounts and sources of donor DNA (chromosomal, amplicon, or replicative plasmid), concentrations of synthetic competence-stimulating peptide, and transformation media were assessed. Results: A semi-defined medium showed much improved results for response to the competence stimulating peptide when compared to rich media. The use of a donor amplicon with large homology flanking regions also provided higher transformation rates. Overall, an increase of transformation efficiencies from 0.001% or less to over 30% was achieved with the developed protocol. We further describe the construction of a markerless mutant based on this high efficiency strategy. Conclusion: We optimized competence development in S. mitis, by use of semi-defined medium and appropriate concentrations of synthetic competence factor. Combined with the use of a large amplicon of donor DNA, this method allowed easy and direct editing of the S. mitis genome, broadening the spectrum of possible downstream applications of natural transformation in this species. PMID:27458432

  20. Working with Schools in Identifying and Overcoming Emotional Barriers to Learning

    ERIC Educational Resources Information Center

    Nash, Poppy; Schlösser, Annette

    2015-01-01

    This paper reports a case study on working closely with a secondary school, to enhance understanding of disruptive behaviour, through the use of bespoke Continuing Professional Development (CPD) materials. This project evolved from the researchers' previous research on the extent to which teachers believe disruptive pupils can control their…

  1. Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

    DTIC Science & Technology

    2015-12-01

    Commons Attribution-NonCommercial License, which permits non- commercial use, distribution, and reproduction , provided the original work is properly cited...www.neurosurgery-online.com Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited replace diseased...CORD NEUROSURGERY VOLUME 77 | NUMBER 4 | OCTOBER 2015 | 605 Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is

  2. Electrical and electronic waste management in China: progress and the barriers to overcome.

    PubMed

    Liu, Xianbing; Tanaka, Masaru; Matsui, Yasuhiro

    2006-02-01

    Serious adverse impacts on the environment and human health from e-waste recycling have occurred in the past and continue to occur in China today, due to a lack of national management strategies. China has made great efforts to face the challenges of the approaching peak increase in the domestic generation of e-waste and the illegal shipment of e-waste from other countries. This study examined recent progress and analysed the main problems associated with this issue in China. It was found that the material and the financial flows of e-waste in China had their own specific characteristics. Nearly 60% of the generated e-wastes were sold to private individual collectors and passed into informal recycling processes. More than 90% of Chinese citizens are reluctant to pay for the recycling of their e-waste. This is due to their traditional understanding that there remained value in these end-of-life products. Regulations concerning e-waste in China have been drafted but their deficiencies are obvious. The extended producer responsibilities (EPR) have been introduced but are not well defined. Eight formal facilities have been planned and are under construction or are in operation along the eastern coast of China but it will be difficult for them to compete with the informal processes for the reasons identified during the study.

  3. Communicating to Overcome Barriers: I Can't Do "One" More Thing!

    ERIC Educational Resources Information Center

    Molony, Terry

    2011-01-01

    While many school psychologists agree that part of the satisfaction in their profession lies in the challenges, dealing with these challenges daily can be exhausting. With NASP's 2010 "Model of Comprehensive and Integrated School Psychological Services" (also known as the NASP Practice Model), school psychologists are challenged to take time to…

  4. Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

    DTIC Science & Technology

    2013-10-01

    Animals received intravenous treatment with Basiliximab (two 10mg IV doses on post-op day 0 and day 4) + MMF (10 mg/kg, BID, IV) + Tacrolimus (0.025mg...op day 0 and day 4) + MMF (10 mg/kg, BID, IV) + Tacrolimus (0.025mg/kg, BID, IV) 21d (Svendsen Laboratory) - Generated, labeled, and shipped

  5. Solid lipid nanoparticles loaded with iron to overcome barriers for treatment of iron deficiency anemia.

    PubMed

    Hosny, Khaled Mohamed; Banjar, Zainy Mohammed; Hariri, Amani H; Hassan, Ali Habiballah

    2015-01-01

    According to the World Health Organization, 46% of the world's children suffer from anemia, which is usually treated with iron supplements such as ferrous sulfate. The aim of this study was to prepare iron as solid lipid nanoparticles, in order to find an innovative way for alleviating the disadvantages associated with commercially available tablets. These limitations include adverse effects on the digestive system resulting in constipation and blood in the stool. The second drawback is the high variability in the absorption of iron and thus in its bioavailability. Iron solid lipid nanoparticles (Fe-SLNs) were prepared by hot homogenization/ultrasonication. Solubility of ferrous sulfate in different solid lipids was measured, and effects of process variables such as the surfactant type and concentration, homogenization and ultrasonication times, and charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release and in vivo pharmacokinetics were studied in rabbits. Results indicated that Fe-SLNs consisted of 3% Compritol 888 ATO, 1% Lecithin, 3% Poloxamer 188, and 0.2% dicetylphosphate, with an average particle size of 25 nm with 92.3% entrapment efficiency. In vivo pharmacokinetic study revealed more than fourfold enhanced bioavailability. In conclusion, Fe-SLNs could be a promising carrier for iron with enhanced oral bioavailability.

  6. Educating Students in Rural America: Capitalizing on Strengths, Overcoming Barriers

    ERIC Educational Resources Information Center

    National Association of State Boards of Education, 2016

    2016-01-01

    In 2004, the National Association of State Boards of Education (NASBE) released a "State Education Standard" focused on the issues and challenges facing rural schools. Ten years later, NASBE facilitated a study group on rural education to discuss what has changed and what new challenges require the attention of state education…

  7. Solid lipid nanoparticles loaded with iron to overcome barriers for treatment of iron deficiency anemia

    PubMed Central

    Hosny, Khaled Mohamed; Banjar, Zainy Mohammed; Hariri, Amani H; Hassan, Ali Habiballah

    2015-01-01

    According to the World Health Organization, 46% of the world’s children suffer from anemia, which is usually treated with iron supplements such as ferrous sulfate. The aim of this study was to prepare iron as solid lipid nanoparticles, in order to find an innovative way for alleviating the disadvantages associated with commercially available tablets. These limitations include adverse effects on the digestive system resulting in constipation and blood in the stool. The second drawback is the high variability in the absorption of iron and thus in its bioavailability. Iron solid lipid nanoparticles (Fe-SLNs) were prepared by hot homogenization/ultrasonication. Solubility of ferrous sulfate in different solid lipids was measured, and effects of process variables such as the surfactant type and concentration, homogenization and ultrasonication times, and charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release and in vivo pharmacokinetics were studied in rabbits. Results indicated that Fe-SLNs consisted of 3% Compritol 888 ATO, 1% Lecithin, 3% Poloxamer 188, and 0.2% dicetylphosphate, with an average particle size of 25 nm with 92.3% entrapment efficiency. In vivo pharmacokinetic study revealed more than fourfold enhanced bioavailability. In conclusion, Fe-SLNs could be a promising carrier for iron with enhanced oral bioavailability. PMID:25609917

  8. Overcoming Barriers to Family Involvement in Title I Schools. Report to Congress.

    ERIC Educational Resources Information Center

    Policy Studies Associates, Inc., Washington, DC.

    Title I of the Elementary and Secondary Education Act as amended by the Improving America's Schools Act (IASA) requires all schools and districts receiving Title I money to engage in an extensive array of activities to build the capacity of parents and school staff to work together in support of students' learning. Title I also requires schools to…

  9. Identifying, Understanding, and Overcoming Barriers to the Use of Clinical Practice Guidelines in Pediatric Oncology

    ClinicalTrials.gov

    2017-02-14

    B-Cell Non-Hodgkin Lymphoma; Chemotherapy-Related Nausea and/or Vomiting; Childhood Acute Myeloid Leukemia; Childhood Burkitt Lymphoma; Childhood Neoplasm; Febrile Neutropenia; Hematopoietic Cell Transplantation Recipient; Recurrent Childhood Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  10. Innovative Strategies to Overcome Biofilm Resistance

    PubMed Central

    Taraszkiewicz, Aleksandra; Fila, Grzegorz; Grinholc, Mariusz; Nakonieczna, Joanna

    2013-01-01

    We review the recent literature concerning the efficiency of antimicrobial photodynamic inactivation toward various microbial species in planktonic and biofilm cultures. The review is mainly focused on biofilm-growing microrganisms because this form of growth poses a threat to chronically infected or immunocompromised patients and is difficult to eradicate from medical devices. We discuss the biofilm formation process and mechanisms of its increased resistance to various antimicrobials. We present, based on data in the literature, strategies for overcoming the problem of biofilm resistance. Factors that have potential for use in increasing the efficiency of the killing of biofilm-forming bacteria include plant extracts, enzymes that disturb the biofilm structure, and other nonenzymatic molecules. We propose combining antimicrobial photodynamic therapy with various antimicrobial and antibiofilm approaches to obtain a synergistic effect to permit efficient microbial growth control at low photosensitizer doses. PMID:23509680

  11. Overcoming catastrophic forgetting in neural networks

    PubMed Central

    Kirkpatrick, James; Pascanu, Razvan; Rabinowitz, Neil; Veness, Joel; Desjardins, Guillaume; Rusu, Andrei A.; Milan, Kieran; Quan, John; Ramalho, Tiago; Grabska-Barwinska, Agnieszka; Hassabis, Demis; Clopath, Claudia; Kumaran, Dharshan; Hadsell, Raia

    2017-01-01

    The ability to learn tasks in a sequential fashion is crucial to the development of artificial intelligence. Until now neural networks have not been capable of this and it has been widely thought that catastrophic forgetting is an inevitable feature of connectionist models. We show that it is possible to overcome this limitation and train networks that can maintain expertise on tasks that they have not experienced for a long time. Our approach remembers old tasks by selectively slowing down learning on the weights important for those tasks. We demonstrate our approach is scalable and effective by solving a set of classification tasks based on a hand-written digit dataset and by learning several Atari 2600 games sequentially. PMID:28292907

  12. T7 replisome directly overcomes DNA damage

    NASA Astrophysics Data System (ADS)

    Sun, Bo; Pandey, Manjula; Inman, James T.; Yang, Yi; Kashlev, Mikhail; Patel, Smita S.; Wang, Michelle D.

    2015-12-01

    Cells and viruses possess several known `restart' pathways to overcome lesions during DNA replication. However, these `bypass' pathways leave a gap in replicated DNA or require recruitment of accessory proteins, resulting in significant delays to fork movement or even cell division arrest. Using single-molecule and ensemble methods, we demonstrate that the bacteriophage T7 replisome is able to directly replicate through a leading-strand cyclobutane pyrimidine dimer (CPD) lesion. We show that when a replisome encounters the lesion, a substantial fraction of DNA polymerase (DNAP) and helicase stay together at the lesion, the replisome does not dissociate and the helicase does not move forward on its own. The DNAP is able to directly replicate through the lesion by working in conjunction with helicase through specific helicase-DNAP interactions. These observations suggest that the T7 replisome is fundamentally permissive of DNA lesions via pathways that do not require fork adjustment or replisome reassembly.

  13. Steric stabilization of nanoparticles with grafted low molecular weight ligands in highly concentrated brines including divalent ions.

    PubMed

    Worthen, Andrew J; Tran, Vu; Cornell, Kevin A; Truskett, Thomas M; Johnston, Keith P

    2016-02-21

    Whereas numerous studies of stabilization of nanoparticles (NPs) in electrolytes have examined biological fluids, the interest has grown recently in media with much higher ionic strengths including seawater and brines relevant to environmental science and subsurface oil and gas reservoirs. Given that electrostatic repulsion is limited at extremely high ionic strengths due to charge screening, we have identified ligands that are well solvated in concentrated brine containing divalent cations and thus provide steric stabilization of silica nanoparticles. Specifically, the hydrodynamic diameter of silica nanoparticles with grafted low molecular weight ligands, a diol ether, [3-(2,3-dihydroxypropoxy)propyl]-trimethoxysilane, and a zwitterionic sulfobetaine, 3-([dimethyl(3-trimethoxysilyl)propyl]ammonio)propane-1-sulfonate, is shown with dynamic light scattering to remain essentially constant, indicating lack of aggregation, at room temperature and up to 80 °C for over 30 days. An extended DLVO model signifies that steric stabilization is strongly dominant against van der Waals attraction for ∼10 nm particles given that these ligands are well solvated even in highly concentrated brine. In contrast, polyethylene glycol oligomers do not provide steric stabilization at elevated temperatures, even at conditions where the ligands are soluble, indicating complicating factors including bridging of the ether oxygens by divalent cations.

  14. Steric hindrance regulated supramolecular assembly between β-cyclodextrin polymer and pyrene for alkaline phosphatase fluorescent sensing.

    PubMed

    Song, Chunxia; Yang, Xiaohai; Wang, Kemin; Wang, Qing; Liu, Jianbo; Huang, Jin; Zhou, Maogui; Guo, Xiaochen

    2016-03-05

    We herein report a strategy for sensitive alkaline phosphatase (ALP) fluorescent sensing based on steric hindrance regulated supramolecular assembly between β-cyclodextrin polymer (polyβ-CD) and pyrene. The fluorescence of pyrene was enhanced more than 10 times through supramolecular assembly with polyβ-CD. The 5'-phosphorylated dsDNA probe with pyrene attached on the 3'-terminal could be cleaved by λ exonuclease (λ exo), yielding pyrene attached on mononucleotides. Pyrene attached on mononucleotides could easily enter the cavity of polyβ-CD, resulting in fluorescence enhancement. When ALP was introduced, it could remove 5'-phosphate groups from dsDNA and then prevented the cleavage of dsDNA. Pyrene attached on dsDNA was difficult to enter the cavity of polyβ-CD because of steric hindrance, resulting in an inconspicuous fluorescence enhancement. Owing to the excellent fluorescence enhancement during steric hindrance regulated supramolecular assembly, excellent performance of the assay method was achieved for ALP with a detection limit of 0.04 Um L(-1). The detection limit was superior or comparable with the reported methods. Besides, this method was simple in design, avoiding double-labeling of probe.

  15. A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs.

    PubMed

    Lu, Mingjian; Kinchen, Jason M; Rossman, Kent L; Grimsley, Cynthia; Hall, Matthew; Sondek, John; Hengartner, Michael O; Yajnik, Vijay; Ravichandran, Kodi S

    2005-02-22

    CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes.

  16. Steric hindrance regulated supramolecular assembly between β-cyclodextrin polymer and pyrene for alkaline phosphatase fluorescent sensing

    NASA Astrophysics Data System (ADS)

    Song, Chunxia; Yang, Xiaohai; Wang, Kemin; Wang, Qing; Liu, Jianbo; Huang, Jin; Zhou, Maogui; Guo, Xiaochen

    2016-03-01

    We herein report a strategy for sensitive alkaline phosphatase (ALP) fluorescent sensing based on steric hindrance regulated supramolecular assembly between β-cyclodextrin polymer (polyβ-CD) and pyrene. The fluorescence of pyrene was enhanced more than 10 times through supramolecular assembly with polyβ-CD. The 5‧-phosphorylated dsDNA probe with pyrene attached on the 3‧-terminal could be cleaved by λ exonuclease (λ exo), yielding pyrene attached on mononucleotides. Pyrene attached on mononucleotides could easily enter the cavity of polyβ-CD, resulting in fluorescence enhancement. When ALP was introduced, it could remove 5‧-phosphate groups from dsDNA and then prevented the cleavage of dsDNA. Pyrene attached on dsDNA was difficult to enter the cavity of polyβ-CD because of steric hindrance, resulting in an inconspicuous fluorescence enhancement. Owing to the excellent fluorescence enhancement during steric hindrance regulated supramolecular assembly, excellent performance of the assay method was achieved for ALP with a detection limit of 0.04 U mL- 1. The detection limit was superior or comparable with the reported methods. Besides, this method was simple in design, avoiding double-labeling of probe.

  17. Liquid marbles prepared from pH-responsive sterically stabilized latex particles.

    PubMed

    Fujii, Syuji; Suzaki, Motomichi; Armes, Steven P; Dupin, Damien; Hamasaki, Sho; Aono, Kodai; Nakamura, Yoshinobu

    2011-07-05

    Submicrometer-sized pH-responsive sterically stabilized polystyrene (PS) latex particles were synthesized by dispersion polymerization in isopropyl alcohol with a poly[2-(diethylamino)ethyl methacrylate]- (PDEA-) based macroinitiator. These PDEA-PS latexes were extensively characterized with respect to their particle size distribution, morphology, chemical composition, and pH-responsive behavior. Millimeter- and centimeter-sized "liquid marbles" with aqueous volumes varying between 15 μL and 2.0 mL were readily prepared by rolling water droplets on the dried PDEA-PS latex powder. The larger liquid marbles adopted nonspherical shapes due to gravitational forces; analysis of this deformation enabled the surface tension to be estimated. Scanning electron microscopy and fluorescence microscopy studies indicated that flocs of the PDEA-PS particles were adsorbed at the surface of these water droplets, leading to stable liquid marbles. The relative mechanical integrity of the liquid marbles prepared from alkaline aqueous solution (pH 10) was higher than those prepared from acidic aqueous solution (pH 2) as judged by droplet roller experiments. These liquid marbles exhibited long-term stability (over 1 h) when transferred onto the surface of liquid water, provided that the solution pH of the subphase was above pH 8. In contrast, the use of acidic solutions led to immediate disintegration of these liquid marbles within 10 min, with dispersal of the PDEA-PS latex particles in the aqueous solution. Thus the critical minimum solution pH required for long-term liquid marble stability correlates closely with the known pK(a) value of 7.3 for the PDEA stabilizer chains. Stable liquid marbles were also successfully prepared from aqueous Gellan gum solution and glycerol.

  18. Steric Effects on the Structures, Reactivity, and Coordination Chemistry of Tris(2-pyridyl)aluminates.

    PubMed

    García-Rodríguez, Raúl; Wright, Dominic S

    2015-10-12

    Introducing substituents in the 6-position of the 2-pyridyl rings of tris(pyridyl)aluminate anions, of the type [EtAl(2-py')3 ](-) (py'=a substituted 2-pyridyl group), has a large impact on their metal coordination characteristics. This is seen most remarkably in the desolvation of the THF solvate [EtAl(6-Me-2-py)3 Li⋅THF] to give the monomer [EtAl(6-Me-2-py)3 Li] (1), containing a pyramidal, three-coordinate Li(+) cation. Similar monomeric complexes are observed for [EtAl(6-CF3 -2-py)3 Li] (2) and [EtAl(6-Br-2-py)3 Li] (3), which contain CF3 and Br substituents (R). This steric influence can be exploited in the synthesis of a new class of terminal Al-OH complexes, as is seen in the controlled hydrolysis of 2 and 3 to give [EtAl(OH)(6-R-2-py)2 ](-) anions, as in the dimer [EtAl(OH)(6-Br-2-py)2 Li]2 (5). Attempts to deprotonate the Al-OH group of 5 using Et2 Zn led only to the formation of the zincate complex [LiZn(6-Br-py)3 ]2 (6), while reactions of the 6-Br substituted 3 and the unsubstituted complex [EtAl(2-py)3 Li] with MeOH give [EtAl(OMe)(6-Br-2-py)2 Li]2 (7) and [EtAl(OMe)(2-py)2 Li]2 (8), respectively, having similar dimeric arrangements to 5. The combined studies presented provide key synthetic methods for the functionalization and elaboration of tris(pyridyl)aluminate ligands.

  19. Solubilization of beclomethasone dipropionate in sterically stabilized phospholipid nanomicelles (SSMs): physicochemical and in vitro evaluations

    PubMed Central

    Sahib, Mohanad Naji; Abdulameer, Shaymaa Abdalwahed; Darwis, Yusrida; Peh, Kok Khiang; Tan, Yvonne Tze Fung

    2012-01-01

    Background The local treatment of lung disorders such as asthma and chronic obstructive pulmonary disease via pulmonary drug delivery offers many advantages over oral or intravenous routes of administration. This is because direct deposition of a drug at the diseased site increases local drug concentrations, which improves the pulmonary receptor occupancy and reduces the overall dose required, therefore reducing the side effects that result from high drug doses. From a clinical point of view, although jet nebulizers have been used for aerosol delivery of water-soluble compounds and micronized suspensions, their use with hydrophobic drugs has been inadequate. Aim: To evaluate the feasibility of sterically stabilized phospholipid nanomicelles (SSMs) loaded with beclomethasone dipropionate (BDP) as a carrier for pulmonary delivery. Methods 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 5000) polymeric micelles containing BDP (BDP-SSMs) were prepared by the coprecipitation and reconstitution method, and the physicochemical and in vitro characteristics of BDP-SSMs were investigated. Results BDP-SSMs were successfully prepared with a content uniformity and reproducibility suitable for pulmonary administration. The maximum solubility of BDP in SSMs was approximately 1300 times its actual solubility. The particle size and zeta potential of BDP-SSMs were 19.89 ± 0.67 nm and −28.03 ± 2.05 mV, respectively. The SSMs system slowed down the release of BDP and all of the aerodynamic values of the aerosolized rehydrated BDP-SSMs were not only acceptable but indicated a significant level of deposition in the lungs. Conclusion The SSM system might be an effective way of improving the therapeutic index of nebulized, poorly soluble corticosteroids. PMID:22393583

  20. Steric environment around acetylcholine head groups of bolaamphiphilic nanovesicles influences the release rate of encapsulated compounds

    PubMed Central

    Stern, Avital; Guidotti, Matteo; Shaubi, Eleonora; Popov, Mary; Linder, Charles; Heldman, Eliahu; Grinberg, Sarina

    2014-01-01

    Two bolaamphiphilic compounds with identical acetylcholine (ACh) head groups, but with different lengths of an alkyl chain pendant adjacent to the head group, as well as differences between their hydrophobic skeleton, were investigated for their ability to self-assemble into vesicles that release their encapsulated content upon hydrolysis of their head groups by acetylcholinesterase (AChE). One of these bolaamphiphiles, synthesized from vernolic acid, has an alkyl chain pendant of five methylene groups, while the other, synthesized from oleic acid, has an alkyl chain pendant of eight methylene groups. Both bolaamphiphiles formed stable spherical vesicles with a diameter of about 130 nm. The ACh head groups of both bolaamphiphiles were hydrolyzed by AChE, but the hydrolysis rate was significantly faster for the bolaamphiphile with the shorter aliphatic chain pendant. Likewise, upon exposure to AChE, vesicles made from the bolaamphiphile with the shorter alkyl chain pendant released their encapsulated content faster than vesicles made from the bolaamphiphile with the longer alkyl chain pendant. Our results suggest that the steric environment around the ACh head group of bolaamphiphiles is a major factor affecting the hydrolysis rate of the head groups by AChE. Attaching an alkyl chain to the bolaamphiphile near the ACh head group allows self-assembled vesicles to form with a controlled release rate of the encapsulated materials, whereas shorter alkyl chains enable a faster head group hydrolysis, and consequently faster release, than longer alkyl chains. This principle may be implemented in the design of bolaamphiphiles for the formation of vesicles for drug delivery with desired controlled release rates. PMID:24531296

  1. Sterically crowded peri-substituted naphthalene phosphines and their PV derivatives.

    PubMed

    Knight, Fergus R; Fuller, Amy L; Bühl, Michael; Slawin, Alexandra M Z; Woollins, J Derek

    2010-07-05

    Three sterically crowded peri-substituted naphthalene phosphines, Nap[PPh(2)][ER] (Nap=naphthalene-1,8-diyl; ER=SEt, SPh, SePh) 1-3, which contain phosphorus and chalcogen functional groups at the peri positions have been prepared. Each phosphine reacts to form a complete series of P(V) chalcogenides Nap[P(E')(Ph(2))(ER)] (E'=O, S, Se). The novel compounds were fully characterised by using X-ray crystallography and multinuclear NMR spectroscopy, IR spectroscopy and MS. X-ray data for 1, 2, nO, nS, nSe (n=1-3) are compared. Eleven molecular structures have been analysed by naphthalene ring torsions, peri-atom displacement, splay angle magnitude, X...E interactions, aromatic ring orientations and quasi-linear arrangements. An increase in the congestion of the peri region following the introduction of heavy chalcogen atoms is accompanied by a general increase in naphthalene distortion. P...E distances increase for molecules that contain bulkier atoms at the peri positions and also when larger chalcogen atoms are bound to phosphorus. The chalcogenides adopt similar conformations that contain a quasi-linear E...P-C fragment, except for 3O, which displays a twist-axial-twist conformation resulting in the formation of a linear O...Se-C alignment. Ab initio MO calculations performed on 2O, 3O, 3S and 3Se reveal Wiberg bond index values of 0.02 to 0.04, which indicates only minor non-bonded interactions; however, calculations on radical cations of 3O, 3S and 3Se reveal increased values (0.14-0.19).

  2. Steric and Electronic Influence of Aryl Isocyanides on the Properties of Iridium(III) Cyclometalates.

    PubMed

    Maity, Ayan; Le, Linh Q; Zhu, Zhuan; Bao, Jiming; Teets, Thomas S

    2016-03-07

    Cyclometalated iridium complexes with efficient phosphorescence and good electrochemical stability are important candidates for optoelectronic devices. Isocyanide ligands are strong-field ligands: when attached to transition metals, they impart larger HOMO-LUMO energy gaps, engender higher oxidative stability at the metal center, and support rugged organometallic complexes. Aryl isocyanides offer more versatile steric and electronic control by selective substitution at the aryl ring periphery. Despite a few reports of alkyl isocyanide of cyclometalated iridium(III), detailed studies on analogous aryl isocyanide complexes are scant. We report the synthesis, photophysical properties, and electrochemical properties of 11 new luminescent cationic biscyclometalated bis(aryl isocyanide)iridium(III) complexes. Three different aryl isocyanides--2,6-dimethylphenyl isocyanide (CNAr(dmp)), 2,6-diisopropylphenyl isocyanide (CNAr(dipp)), and 2-naphthyl isocyanide (CNAr(nap))--were combined with four cyclometalating ligands with differential π-π* energies--2-phenylpyridine (ppy), 2,4-difluorophenylpyridine (F2ppy), 2-benzothienylpyridine (btp), and 2-phenylbenzothiazole (bt). Five of them were crystallographically characterized. All new complexes show wide redox windows, with reduction potentials falling in a narrow range of -2.02 to -2.37 V and oxidation potentials spanning a wider range of 0.97-1.48 V. Efficient structured emission spans from the blue region for [(F2ppy)2Ir(CNAr)2]PF6 to the orange region for [(btp)2Ir(CNAr)2]PF6, demonstrating that isocyanide ligands can support redox-stable luminescent complexes with a range of emission colors. Emission quantum yields were generally high, reaching a maximum of 0.37 for two complexes, whereas btp-ligated complexes had quantum yields below 1%. The structure of the CNAr ligand has a minimal effect on the photophysical properties, which are shown to arise from ligand-centered excited states with very little contribution from

  3. Permissivity of the biphenyl-specific aerobic bacterial metabolic pathway towards analogues with various steric requirements.

    PubMed

    Overwin, Heike; Standfuß-Gabisch, Christine; González, Myriam; Méndez, Valentina; Seeger, Michael; Reichelt, Joachim; Wray, Victor; Hofer, Bernd

    2015-09-01

    It has repeatedly been shown that aryl-hydroxylating dioxygenases do not possess a very high substrate specificity. To gain more insight into this phenomenon, we examined two powerful biphenyl dioxygenases, the well-known wild-type enzyme from Burkholderia xenovorans LB400 (BphA-LB400) and a hybrid enzyme, based on a dioxygenase from Pseudomonas sp. B4-Magdeburg (BphA-B4h), for their abilities to dioxygenate a selection of eight biphenyl analogues in which the second aromatic ring was replaced by aliphatic as well as aliphatic/aromatic moieties, reflecting a variety of steric requirements. Interestingly, both enzymes were able to catalyse transformation of almost all of these compounds. While the products formed were identical, major differences were observed in transformation rates. In most cases, BphA-B4h proved to be a significantly more powerful catalyst than BphA-LB400. NMR characterization of the reaction products showed that the metabolite obtained from biphenylene underwent angular dioxygenation, whereas all other compounds were subject to lateral dioxygenation at ortho and meta carbons. Subsequent growth studies revealed that both dioxygenase source strains were able to utilize several of the biphenyl analogues as sole sources of carbon and energy. Therefore, prototype BphBCD enzymes of the biphenyl degradative pathway were examined for their ability to further catabolize the lateral dioxygenation products. All of the ortho- and meta-hydroxylated compounds were converted to acids, showing that this pathway is quite permissive, enabling catalysis of the turnover of a fairly wide variety of metabolites.

  4. Overcoming the obstacles: Life stories of scientists with learning disabilities

    NASA Astrophysics Data System (ADS)

    Force, Crista Marie

    Scientific discovery is at the heart of solving many of the problems facing contemporary society. Scientists are retiring at rates that exceed the numbers of new scientists. Unfortunately, scientific careers still appear to be outside the reach of most individuals with learning disabilities. The purpose of this research was to better understand the methods by which successful learning disabled scientists have overcome the barriers and challenges associated with their learning disabilities in their preparation and performance as scientists. This narrative inquiry involved the researcher writing the life stories of four scientists. These life stories were generated from extensive interviews in which each of the scientists recounted their life histories. The researcher used narrative analysis to "make sense" of these learning disabled scientists' life stories. The narrative analysis required the researcher to identify and describe emergent themes characterizing each scientist's life. A cross-case analysis was then performed to uncover commonalities and differences in the lives of these four individuals. Results of the cross-case analysis revealed that all four scientists had a passion for science that emerged at an early age, which, with strong drive and determination, drove these individuals to succeed in spite of the many obstacles arising from their learning disabilities. The analysis also revealed that these scientists chose careers based on their strengths; they actively sought mentors to guide them in their preparation as scientists; and they developed coping techniques to overcome difficulties and succeed. The cross-case analysis also revealed differences in the degree to which each scientist accepted his or her learning disability. While some demonstrated inferior feelings about their successes as scientists, still other individuals revealed feelings of having superior abilities in areas such as visualization and working with people. These individuals revealed

  5. Overcoming Breakdowns and Engaging the Public

    NASA Astrophysics Data System (ADS)

    Bowman, T. E.

    2012-12-01

    With strong climate science evidence readily available, why do major segments of the public remain disengaged? Decades of social science research and practical communications experience indicate that prioritizing and structuring information, choosing appropriate messengers, and adapting to audience interests and learning styles are vital, yet often ignored criteria. This session will explore key differences between communications models within the science community and effective outreach to non-scientist audiences. Here, prioritizing goals, understanding preconceptions and identifying intervention opportunities require careful examination. "Public engagement" is defined as encouraging and enabling people to make informed choices on their own behalf. Crucial barriers identified in economics, political psychology and audience segmentation research will be addressed, and recommendations for more effective engagement will emerge including: defining realistic goals, simplifying science content accurately, avoiding values conflicts that prevent learning, enlisting trusted messengers, and matching a call to action to the scale of the challenge in ways people can embrace.

  6. Mass-induced sea level variations in the Red Sea from GRACE, steric-corrected altimetry, in situ bottom pressure records, and hydrographic observations

    NASA Astrophysics Data System (ADS)

    Feng, W.; Lemoine, J.-M.; Zhong, M.; Hsu, H. T.

    2014-08-01

    An annual amplitude of ∼18 cm mass-induced sea level variations (SLV) in the Red Sea is detected from the Gravity Recovery and Climate Experiment (GRACE) satellites and steric-corrected altimetry from 2003 to 2011. The annual mass variations in the region dominate the mean SLV, and generally reach maximum in late January/early February. The annual steric component of the mean SLV is relatively small (<3 cm) and out of phase of the mass-induced SLV. In situ bottom pressure records at the eastern coast of the Red Sea validate the high mass variability observed by steric-corrected altimetry and GRACE. In addition, the horizontal water mass flux of the Red Sea estimated from GRACE and steric-corrected altimetry is validated by hydrographic observations.

  7. The immunological barriers to xenotransplantation.

    PubMed

    Vadori, M; Cozzi, E

    2015-10-01

    The availability of cells, tissues and organs from a non-human species such as the pig could, at least in theory, meet the demand of organs necessary for clinical transplantation. At this stage, the important goal of getting over the first year of survival has been reported for both cellular and solid organ xenotransplantation in relevant preclinical primate models. In addition, xenotransplantation is already in the clinic as shown by the broad use of animal-derived medical devices, such as bioprosthetic heart valves and biological materials used for surgical tissue repair. At this stage, however, prior to starting a wide-scale clinical application of xenotransplantation of viable cells and organs, the important obstacle represented by the humoral immune response will need to be overcome. Likewise, the barriers posed by the activation of the innate immune system and coagulative pathway will have to be controlled. As far as xenogeneic nonviable xenografts, increasing evidence suggests that considerable immune reactions, mediated by both innate and adaptive immunity, take place and influence the long-term outcome of xenogeneic materials in patients, possibly precluding the use of bioprosthetic heart valves in young individuals. In this context, the present article provides an overview of current knowledge on the immune processes following xenotransplantation and on the possible therapeutic interventions to overcome the immunological drawbacks involved in xenotransplantation.

  8. Puncture detecting barrier materials

    DOEpatents

    Hermes, R.E.; Ramsey, D.R.; Stampfer, J.F.; Macdonald, J.M.

    1998-03-31

    A method and apparatus for continuous real-time monitoring of the integrity of protective barrier materials, particularly protective barriers against toxic, radioactive and biologically hazardous materials has been developed. Conductivity, resistivity or capacitance between conductive layers in the multilayer protective materials is measured by using leads connected to electrically conductive layers in the protective barrier material. The measured conductivity, resistivity or capacitance significantly changes upon a physical breach of the protective barrier material. 4 figs.

  9. Puncture detecting barrier materials

    DOEpatents

    Hermes, Robert E.; Ramsey, David R.; Stampfer, Joseph F.; Macdonald, John M.

    1998-01-01

    A method and apparatus for continuous real-time monitoring of the integrity of protective barrier materials, particularly protective barriers against toxic, radioactive and biologically hazardous materials has been developed. Conductivity, resistivity or capacitance between conductive layers in the multilayer protective materials is measured by using leads connected to electrically conductive layers in the protective barrier material. The measured conductivity, resistivity or capacitance significantly changes upon a physical breach of the protective barrier material.

  10. Understanding and overcoming metformin gastrointestinal intolerance.

    PubMed

    Bonnet, Fabrice; Scheen, André

    2017-04-01

    Metformin is the most widely prescribed drug for patients with type 2 diabetes mellitus and the first-line pharmacological option as supported by multiple international guidelines, yet a rather large proportion of patients cannot tolerate metformin in adequate amounts because of its associated gastrointestinal (GI) adverse events (AEs). GI AEs typically encountered with metformin therapy include diarrhoea, nausea, flatulence, indigestion, vomiting and abdominal discomfort, with diarrhoea and nausea being the most common. Although starting at a low dose and titrating slowly may help prevent some GI AEs associated with metformin, some patients are unable to tolerate metformin at all and it may also be difficult to convince patients to start metformin again after a bout of GI AEs. Despite this clinical importance, the underlying mechanisms of the GI intolerance associated with metformin are poorly known. In the present review, we discuss: the epidemiology of metformin-associated GI intolerance and its underlying mechanisms; genotype variability and associated factors affecting metformin GI intolerance, such as comorbidities, co-medications and bariatric surgery; clinical consequences and therapeutic strategies to overcome metformin GI intolerance. These strategies include appropriate titration of immediate-release metformin, use of extended-release metformin, the promise of delayed-release metformin and gut microbiome modulators, as well as alternative pharmacological therapies when metformin cannot be tolerated at all. Given the available data, all efforts should be made to maintain metformin before considering a shift to another drug therapy.

  11. Overcoming Old in Age-Friendliness

    PubMed Central

    Lindenberg, J.; Westendorp, R.G.J.

    2015-01-01

    In this article, we explore views on an age-friendly space in the Netherlands by analysing the responses of older individuals (N = 54) in focus groups and by examining the perspectives around an age-friendly zone in the Netherlands, Parkstad Limburg. We found that a central issue in the wishes for living at a later age are adjustments to envisioned physical limitations that come with the ageing process; this includes adjustments to ensure safety, accessibility and mobility, in order to facilitate older individuals' efforts to stay engaged with the world around them. In their wishes, the older participants constructed ideal dwelling places that closely resembled a senior home, but at the same time they rejected wishing to live in a place that was identified as a senior home. We explain this paradox by the representation of such a space as being for old people, i.e. needy older individuals, which was not how the older participants wished to be identified. We conclude that the conception of age-friendly environments will have to face the difficult challenge of overcoming the association with old age, while simultaneously taking into account adjustments that signify and relate to the ageing process and that seem inescapably tied to oldness. PMID:26028795

  12. NANOPREPARATIONS TO OVERCOME MULTIDRUG RESISTANCE IN CANCER

    PubMed Central

    Patel, Niravkumar R.; Pattni, Bhushan S.; Abouzeid, Abraham H.; Torchilin, Vladimir P.

    2013-01-01

    Multidrug resistance is the most widely exploited phenomenon by which cancer eludes chemotherapy. Broad variety of factors, ranging from the cellular ones, such as over-expression of efflux transporters, defective apoptotic machineries, and altered molecular targets, to the physiological factors such as higher interstitial fluid pressure, low extracellular pH, and formation of irregular tumor vasculature are responsible for multidrug resistance. A combination of various undesirable factors associated with biological surroundings together with poor solubility and instability of many potential therapeutic small & large molecules within the biological systems and systemic toxicity of chemotherapeutic agents has necessitated the need for nano-preparations to optimize drug delivery. The physiology of solid tumors presents numerous challenges for successful therapy. However, it also offers unique opportunities for the use of nanotechnology. Nanoparticles, up to 400 nm in size, have shown great promise for carrying, protecting and delivering potential therapeutic molecules with diverse physiological properties. In this review, various factors responsible for the MDR and the use of nanotechnology to overcome the MDR, the use of spheroid culture as well as the current technique of producing micro tumor tissues in vitro are discussed in detail. PMID:23973912

  13. Barriers to Healthier Eating in a Disadvantaged Community

    ERIC Educational Resources Information Center

    O'Neill, Martin; Rebane, Deanne; Lester, Carolyn

    2004-01-01

    Objective: The research objective was to identify how healthy eating was understood in a disadvantaged community and how barriers to healthy eating might be overcome. Design: Participatory action research. Setting: Communities in Gurnos, Merthyr Tydfil, one of the most deprived areas in the UK. Method: Trainees on a participative methods course…

  14. Dinitrogen activation in sterically-hindered three-coordinate transition metal complexes.

    PubMed

    Christian, Gemma; Driver, Jenni; Stranger, Robert

    2003-01-01

    Dinuclear metal systems based on sterically-hindered, three-coordinate transition metal complexes of the type ML3 where the ancillary ligands L comprise bulky organic substituents, hold great promise synthetically for the activation and scission of small, multiply-bonded molecules such as N2, NO and N2O. In this study we have employed density functional methods to identify the metal/ligand combinations which achieve optimum activation and/or cleavage of N2. Strong pi donor ligands such as NH2 and OH are found to produce the greatest level of activation based on N-N bond lengths in the intermediate dimer complex, L3Mo(mu-N2)MoL3, whereas systems containing the weak or non-pi donor ligands NH3, PH3, OH2 and SH2 are found to be thermodynamically unfavourable for N2 activation. In the case of the Mo-NH2 and W-NH2 systems, a fragment bonding analysis reveals that the orientation of the amide ligands around the metal is important in determining both the spin state and the extent of dinitrogen activation in the intermediate dimer. For both systems, an intermediate dimer structure where one of the NH2 ligands on each metal is rotated 90 degrees relative to the other ligands, is more activated than the structure in which the NH2 ligands are trigonally disposed around the metals. The level of activation is found to be very sensitive to the electronic configuration of the metal with d3 metal ions delivering the best activation along any one transition series. In particular, strong activation or cleavage of N2 was calculated for the third row d3 metals systems involving Ta(II), W(III) and Re(IV), with the level of activation decreasing as the nuclear charge on the metal increases. This trend in activation reflects the size of the valence 5d orbitals and consequently, the capacity of the metal to back donate into the dinitrogen pi* orbitals.

  15. Electronic and steric influences of pendant amine groups on the protonation of molybdenum bis (dinitrogen) complexes

    SciTech Connect

    Labios, Liezel A.; Heiden, Zachariah M.; Mock, Michael T.

    2015-05-04

    The synthesis of a series of PEtPNRR' (PEtPNRR' = Et₂PCH₂CH₂P(CH₂NRR')₂, R = H, R' = Ph or 2,4-difluorophenyl; R = R' = Ph or iPr) diphosphine ligands containing mono- and disubstituted pendant amine groups, and the preparation of their corresponding molybdenum bis(dinitrogen) complexes trans-Mo(N₂)₂(PMePh₂)₂(PEtPNRR') is described. In situ IR and multinuclear NMR spectroscopic studies monitoring the stepwise addition of (HOTf) to trans-Mo(N₂)₂(PMePh₂)₂(PEtPNRR') complexes in THF at -40 °C show that the electronic and steric properties of the R and R' groups of the pendant amines influence whether the complexes are protonated at Mo, a pendant amine, a coordinated N2 ligand, or a combination of these sites. For example, complexes containing mono-aryl substituted pendant amines are protonated at Mo and pendant amine to generate mono- and dicationic Mo–H species. Protonation of the complex containing less basic diphenyl-substituted pendant amines exclusively generates a monocationic hydrazido (Mo(NNH₂)) product, indicating preferential protonation of an N₂ ligand. Addition of HOTf to the complex featuring more basic diisopropyl amines primarily produces a monocationic product protonated at a pendant amine site, as well as a trace amount of dicationic Mo(NNH₂) product that contain protonated pendant amines. In addition, trans-Mo(N₂)₂(PMePh₂)₂(depe) (depe = Et₂PCH₂CH₂PEt₂) without a pendant amine was synthesized and treated with HOTf, generating a monocationic Mo(NNH₂) product. Protonolysis experiments conducted on select complexes in the series afforded trace amounts of NH₄⁺. Computational analysis of the series of trans-Mo(N₂)₂(PMePh₂)₂(PEtPNRR') complexes provides further insight into the proton affinity values of the metal center, N₂ ligand, and pendant amine sites to rationalize

  16. Acylmethyl(aryl)tellurium(IV,II) derivatives: intramolecular secondary bonding and steric rigidity.

    PubMed

    Chauhan, Ashok K S; Singh, Puspendra; Srivastava, Ramesh C; Duthie, Andrew; Voda, Andreea

    2008-08-14

    Electrophilic substitution of acylmethanes (methyl ketones), RCOCH3 (R = i-Pr, 1; Et, 2; Me, 3) with aryltellurium trichlorides, ArTeCl3 (Ar = 1-C10H7, Np, A; 2,4,6-Me3C6H2, Mes, B; 4-MeOC6H4, Anisyl, C) under mild conditions affords the corresponding acylmethyl(aryl)tellurium dichlorides (RCOCH2)ArTeCl2. Reduction of the dichlorides, gives tellurides, (i-PrCOCH2)ArTe, 1A-1C, which give the corresponding dihalides, (i-PrCOCH2)ArTeX2 (X = Cl, 1Aa-1Ca; Br, 1Ab-1Cb; I, 1Ac-1Cc) when reacted in situ with SO2Cl2, Br2 or I2. The unsymmetric tellurides are labile towards disproportionation and attempts to obtain them lead to the isolation of Ar2Te2 except in the case of (i-PrCOCH2)MesTe (1B), which represents an interesting example of a kinetically stable aryl(alkyl)telluride. All the dihalomesityltellurium(IV) derivatives show separate 1H and 13C NMR signals for the ortho methyls irrespective of the sizes of R and X ligands. The telluride, 1B with free rotation about Te-C(mesityl) bond shows, like the unsymmetric diorganotellurium(IV) dihalides, only one 125Te NMR signal. The 1,4-chelating behavior of the acyl ligand among diorganotellurium(IV) compounds is inferred from the X-ray diffraction data for 1Aa, 1Ac, 1Ba, 1Bb, 1cA and 1Cc which are indicative of the presence of intramolecular Te...O secondary bonding interactions (SBIs) at least in the solid state. As a consequence, steric repulsion in case of the mesityltellurium(IV) derivatives, 1Ba and 1Bb, reaches the threshold so as to cause loss of two-fold rotational symmetry of the mesityl group about the Te-C(mesityl) bond axis. Intermolecular C-HO...O H-bonding interactions appears to stabilize such an orientation of the aryl ligand at least in the solid state.

  17. The Barriers Project.

    ERIC Educational Resources Information Center

    Confederation Coll. of Applied Arts and Technology, Thunder Bay (Ontario).

    In 1987, the Barriers Project was initiated by Confederation College of Applied Arts and Technology to engage 31 selected community colleges in Canada in an organized self-appraisal of institutional barriers to the enrollment of part-time credit students. From the outset, colleges were encouraged to limit their investigation to barriers over which…

  18. Development of the Motivators of and Barriers to Health-Smart Behaviors Inventory

    ERIC Educational Resources Information Center

    Tucker, Carolyn M.; Rice, Kenneth G.; Hou, Wei; Kaye, Lillian B.; Nolan, Sarah E. M.; Grandoit, Delphia J.; Gonzales, Lucia; Smith, Mary B.; Desmond, Frederic F.

    2011-01-01

    The Motivators of and Barriers to Health-Smart Behaviors Inventory (MB-HSBI) was developed for use in identifying self-reported motivators of and barriers to the following health-promoting behaviors (called "health-smart behaviors") that should occur daily to help promote health and overcome illnesses/diseases: eating a healthy…

  19. Barriers and Strategies for Success for American Indian College Students: A Review

    ERIC Educational Resources Information Center

    Keith, Jill F.; Stastny, Sherri N.; Brunt, Ardith

    2016-01-01

    American Indian and Alaska Native students have a significantly lower college graduation rate than that of other ethnic groups in the United States. These students often face a variety of barriers to the completion of their education. Overcoming barriers for the achievement of an advanced education takes commitment, hard work, and dedication on…

  20. Mass-induced sea level variations in the Red Sea from steric-corrected altimetry, GRACE, in-situ bottom pressure records, and hydrographic observations

    NASA Astrophysics Data System (ADS)

    Feng, Wei; Lemoine, Jean-Michel; Zhong, Min; Xu, Houze

    2014-05-01

    An annual amplitude of ~18 cm mass-induced sea level variations (SLV) in the Red Sea is detected from steric-corrected altimetry and the Gravity Recovery and Climate Experiment (GRACE) satellites from 2003 to 2011, which dominates the mean sea level in the region. Seawater mass variations here generally reach maximum in late January/early February. The steric component of SLV calculated from oceanographic temperature and salinity data is relatively small and peaks about seven months later than mass variations. The phase difference between the steric SLV and the mass-induced SLV indicates that when the Red Sea gains the mass from inflow water in winter, the steric SLV fall, and vice versa in summer. In-situ bottom pressure records in the eastern coast of the Red Sea validate the high mass variability observed by steric-corrected altimetry and GRACE. Furthermore, we compare the horizontal water mass flux in the Red Sea from steric-corrected altimetry and GRACE with that estimated from hydrographic observations.

  1. Nested barriers to low-carbon infrastructure investment

    NASA Astrophysics Data System (ADS)

    Granoff, Ilmi; Hogarth, J. Ryan; Miller, Alan

    2016-12-01

    Low-carbon, 'green' economic growth is necessary to simultaneously improve human welfare and avoid the worst impacts of climate change and environmental degradation. Infrastructure choices underpin both the growth and the carbon intensity of the economy. This Perspective explores the barriers to investing in low-carbon infrastructure and some of the policy levers available to overcome them. The barriers to decarbonizing infrastructure 'nest' within a set of barriers to infrastructure development more generally that cause spending on infrastructure--low-carbon or not--to fall more than 70% short of optimal levels. Developing countries face additional barriers such as currency and political risks that increase the investment gap. Low-carbon alternatives face further barriers, such as commercialization risk and financial and public institutions designed for different investment needs. While the broader barriers to infrastructure investment are discussed in other streams of literature, they are often disregarded in literature on renewable energy diffusion or climate finance, which tends to focus narrowly on the project costs of low- versus high-carbon options. We discuss how to overcome the barriers specific to low-carbon infrastructure within the context of the broader infrastructure gap.

  2. Space patrol: Variants of the optical barrier scheme

    NASA Astrophysics Data System (ADS)

    Akhmetshin, R. Z.

    2013-07-01

    Different variants of the space patrol system to be designed for discovering and cataloging space objects hazardous for the Earth have been investigated. The basic idea of this system is to create an optical barrier using the telescopes deployed in a heliocentric orbit. Difficulties (as well as ways of overcoming them) of this program are analyzed, associated with form and position of the orbit of a space object relative to the patrol spacecraft, determination of orbit parameters, and mutual motion of space objects and the telescopes on spacecraft. The barrier's schemes with scanning vertical or horizontal belts are considered. Some examples of observational conditions are presented for space objects crossing the barrier region: angular positions, velocities, distances, and numbers of days during which they are observed in the barrier region. The barrier's characteristics are given for telescopes deployed in the orbits of the Earth and Venus.

  3. The Need for More Research on Language Barriers in Health Care: A Proposed Research Agenda

    PubMed Central

    Jacobs, Elizabeth; Chen, Alice HM; Karliner, Leah S; Agger-Gupta, Niels; Mutha, Sunita

    2006-01-01

    Many U.S. residents who speak little English may face language barriers when seeking health care. This article describes what is currently known about language barriers in health care and outlines a research agenda based on mismatches between the current state of knowledge of language barriers and what health care stakeholders need to know. Three broad areas needing more research are discussed: the ways in which language barriers affect health and health care, the efficacy of linguistic access service interventions, and the costs of language barriers and efforts to overcome them. In each of these areas, we outline specific research questions and recommendations. PMID:16529570

  4. Barriers to pain management: focus on opioid therapy.

    PubMed

    Zuccaro, Stefano Maria; Vellucci, Renato; Sarzi-Puttini, Piercarlo; Cherubino, Paolo; Labianca, Roberto; Fornasari, Diego

    2012-02-22

    Despite the availability of effective pain treatments, there are numerous barriers to effective management resulting in a large proportion of patients not achieving optimal pain control. Chronic pain is inadequately treated because of a combination of cultural, societal, educational, political and religious constraints. The consequences of inadequately treated pain are physiological and psychological effects on the patient, as well as socioeconomic implications. Unreasonable failure to treat pain is viewed as unethical and an infringement of basic human rights. The numerous barriers to the clinical management of pain vary depending on whether they are viewed from the standpoint of the patient, the physician, or the institution. Identification and acknowledgement of the barriers involved are the first steps to overcoming them. Successful initiatives to overcome patient, physician and institutional barriers need to be multifaceted in their approach. Multidisciplinary initiatives to improve pain management include dissemination of community-based information, education and awareness programmes to attempt to change attitudes towards pain treatment. A better awareness and insight into the problems caused by unrelieved pain and greater knowledge about the efficacy and tolerability of available pain management options should enable physicians to seek out and adhere to treatment guidelines, and participate in interventional and educational programmes designed to improve pain management, and for institutions to implement the initiatives required. Although much work is underway to identify and resolve the issues in pain management, many patients still receive inadequate treatment. Continued effort is required to overcome the known barriers to effective pain management.

  5. Overcoming regulatory and economic challenges facing pharmacogenomics.

    PubMed

    Cohen, Joshua P

    2012-09-15

    The number of personalized medicines and companion diagnostics in use in the United States has gradually increased over the past decade, from a handful of medicines and tests in 2001 to several dozen in 2011. However, the numbers have not reached the potential hoped for when the human genome project was completed in 2001. Significant clinical, regulatory, and economic barriers exist and persist. From a regulatory perspective, therapeutics and companion diagnostics are ideally developed simultaneously, with the clinical significance of the diagnostic established using data from the clinical development program of the corresponding therapeutic. Nevertheless, this is not (yet) happening. Most personalized medicines are personalized post hoc, that is, a companion diagnostic is developed separately and approved after the therapeutic. This is due in part to a separate and more complex regulatory process for diagnostics coupled with a lack of clear regulatory guidance. More importantly, payers have placed restrictions on reimbursement of personalized medicines and their companion diagnostics, given the lack of evidence on the clinical utility of many tests. To achieve increased clinical adoption of diagnostics and targeted therapies through more favorable reimbursement and incorporation in clinical practice guidelines, regulators will need to provide unambiguous guidance and manufacturers will need to bring more and better clinical evidence to the market place.

  6. Extremal surface barriers

    NASA Astrophysics Data System (ADS)

    Engelhardt, Netta; Wall, Aron C.

    2014-03-01

    We present a generic condition for Lorentzian manifolds to have a barrier that limits the reach of boundary-anchored extremal surfaces of arbitrary dimension. We show that any surface with nonpositive extrinsic curvature is a barrier, in the sense that extremal surfaces cannot be continuously deformed past it. Furthermore, the outermost barrier surface has nonnegative extrinsic curvature. Under certain conditions, we show that the existence of trapped surfaces implies a barrier, and conversely. In the context of AdS/CFT, these barriers imply that it is impossible to reconstruct the entire bulk using extremal surfaces. We comment on the implications for the firewall controversy.

  7. Steric and electrostatic effects in DNA synthesis by the SOS-induced DNA polymerases II and IV of Escherichia coli.

    PubMed

    Silverman, Adam P; Jiang, Qingfei; Goodman, Myron F; Kool, Eric T

    2007-12-04

    The SOS-induced DNA polymerases II and IV (pol II and pol IV, respectively) of Escherichia coli play important roles in processing lesions that occur in genomic DNA. Here we study how electrostatic and steric effects play different roles in influencing the efficiency and fidelity of DNA synthesis by these two enzymes. These effects were probed by the use of nonpolar shape analogues of thymidine, in which substituted toluenes replace the polar thymine base. We compared thymine with nonpolar analogues to evaluate the importance of hydrogen bonding in the polymerase active sites, while we used comparisons among a set of variably sized thymine analogues to measure the role of steric effects in the two enzymes. Steady-state kinetics measurements were carried out to evaluate activities for nucleotide insertion and extension. The results showed that both enzymes inserted nucleotides opposite nonpolar template bases with moderate to low efficiency, suggesting that both polymerases benefit from hydrogen bonding or other electrostatic effects involving the template base. Surprisingly, however, pol II inserted nonpolar nucleotide (dNTP) analogues into a primer strand with high (wild-type) efficiency, while pol IV handled them with an extremely low efficiency. Base pair extension studies showed that both enzymes bypass non-hydrogen-bonding template bases with moderately low efficiency, suggesting a possible beneficial role of minor groove hydrogen bonding interactions at the N-1 position. Measurement of the two polymerases' sensitivity to steric size changes showed that both enzymes were relatively flexible, yielding only small kinetic differences with increases or decreases in nucleotide size. Comparisons are made to recent data for DNA pol I (Klenow fragment), the archaeal polymerase Dpo4, and human pol kappa.

  8. Conversion of Sterically Demanding α,α-Disubstituted Phenylacetonitriles by the Arylacetonitrilase from Pseudomonas fluorescens EBC191

    PubMed Central

    Baum, Stefanie; Williamson, Dael S.; Sewell, Trevor

    2012-01-01

    The nitrilase from Pseudomonas fluorescens EBC191 converted 2-methyl-2-phenylpropionitrile, which contains a quaternary carbon atom in the α-position toward the nitrile group, and also similar sterically demanding substrates, such as 2-hydroxy-2-phenylpropionitrile (acetophenone cyanohydrin) or 2-acetyloxy-2-methylphenylacetonitrile. 2-Methyl-2-phenylpropionitrile was hydrolyzed to almost stoichiometric amounts of the corresponding acid. Acetophenone cyanohydrin was transformed to the corresponding acid (atrolactate) and amide (atrolactamide) at a ratio of about 3.4:1. The (R)-acid and the (S)-amide were formed preferentially from acetophenone cyanohydrin. A homology model of the nitrilase suggested that steric hindrance with amino acid residue Tyr54 could impair the binding or conversion of sterically demanding substrates. Therefore, several enzyme variants that carried mutations in the respective residues were generated and subsequently analyzed for the substrate specificity and enantioselectivity of the reactions. Enzyme variants that demonstrated increased relative activities for the conversion of acetophenone cyanohydrin were identified. The chiral analysis of these reactions demonstrated peculiar reaction kinetics, which suggested that the enzyme variants converted the nonpreferred (S)-enantiomer of acetophenone cyanohydrin with a higher reaction rate than that of the (preferred) (R)-enantiomer. Recombinant whole-cell catalysts that simultaneously produced the nitrilase from P. fluorescens EBC191 and a plant-derived (S)-oxynitrilase from cassava (Manihot esculenta) converted acetophenone plus cyanide at pH 4.5 to (S)-atrolactate and (S)-atrolactamide. These recombinant cells are promising catalysts for the synthesis of stable chiral quaternary carbon centers from ketones. PMID:22020513

  9. A sterically expanded "constrained geometry catalyst" for highly active olefin polymerization and copolymerization: an unyielding comonomer effect.

    PubMed

    Irwin, Levi J; Reibenspies, Joseph H; Miller, Stephen A

    2004-12-29

    The 14 A octamethyloctahydrodibenzofluorene moiety has been incorporated into a sterically expanded constrained geometry catalyst, Me2Si(eta1-C29H36)(eta1-N-tBu)ZrCl2.OEt2 (1). The solid-state structure suggests that the activated olefin polymerization catalyst is quite spatially accessible, rationalizing its extraordinary reactivity toward alpha-olefins. 1/MAO (MAO = methylaluminoxane) can be more reactive toward alpha-olefins than toward ethylene and exhibit activities that are linearly and continuously proportional to 4-methyl-1-pentene or 1-octene concentration in their copolymerizations with ethylene.

  10. An S(N)Ar approach to sterically hindered ortho-alkoxybenzaldehydes for the synthesis of olefin metathesis catalysts.

    PubMed

    Engle, Keary M; Luo, Shao-Xiong; Grubbs, Robert H

    2015-04-17

    A three-step procedure has been developed for preparing ortho-alkoxybenzaldehydes from ortho-fluorobenzaldehydes that tolerates the use of sterically hindered sodium alkoxide nucleophiles. The protocol is modular and operationally convenient. The ortho-alkoxybenzaldehyde products can be converted in one additional step to ortho-alkoxystyrenes by a Wittig reaction. These styrenes are precursors to the chelating benzylidene moiety in a proposed series of novel ruthenium complexes for use in olefin metathesis. Chelation with three representative styrenes has been demonstrated.

  11. Sterically-controlled intermolecular Friedel-Crafts acylation with twisted amides via selective N-C cleavage under mild conditions.

    PubMed

    Liu, Yongmei; Meng, Guangrong; Liu, Ruzhang; Szostak, Michal

    2016-05-21

    Highly chemoselective Friedel-Crafts acylation with twisted amides under mild conditions is reported for the first time. The reaction shows high functional group tolerance, obviating the need for preformed sensitive organometallic reagents and expensive transition metal catalysts. The high reactivity of amides is switched on by ground-state steric distortion to disrupt the amide bond nN→πCO* resonance as a critical design feature. Conceptually, this new acid-promoted mechanism of twisted amides provides direct access to bench-stable acylating reagents under mild, metal-free conditions.

  12. Toward the understanding of chemical absorption processes for post-combustion capture of carbon dioxide: electronic and steric considerations from the kinetics of reactions of CO2(aq) with sterically hindered amines.

    PubMed

    Conway, William; Wang, Xiaoguang; Fernandes, Debra; Burns, Robert; Lawrance, Geoffrey; Puxty, Graeme; Maeder, Marcel

    2013-01-15

    The present study reports (a) the determination of both the kinetic rate constants and equilibrium constants for the reaction of CO(2)(aq) with sterically hindered amines and (b) an attempt to elucidate a fundamental chemical understanding of the relationship between the amine structure and chemical properties of the amine that are relevant for postcombustion capture of CO(2) (PCC) applications. The reactions of CO(2)(aq) with a series of linear and methyl substituted primary amines and alkanolamines have been investigated using stopped-flow spectrophotometry and (1)H NMR measurements at 25.0 °C. The specific mechanism of absorption for each of the amines, that is CO(2) hydration and/or carbamate formation, is examined and, based on the mechanism, the kinetic and equilibrium constants for the formation of carbamic acid/carbamates, including protonation constants of the carbamate, are reported for amines that follow this pathway. A Brønsted correlation relating the kinetic rate constants and equilibrium constants for the formation of carbamic acid/carbamates with the protonation constant of the amine is reported. Such a relationship facilitates an understanding of the effects of steric and electronic properties of the amine toward its reactivity with CO(2). Further, such relationships can be used to guide the design of new amines with improved properties relevant to PCC applications.

  13. Multilayer moisture barrier

    DOEpatents

    Pankow, Joel W; Jorgensen, Gary J; Terwilliger, Kent M; Glick, Stephen H; Isomaki, Nora; Harkonen, Kari; Turkulainen, Tommy

    2015-04-21

    A moisture barrier, device or product having a moisture barrier or a method of fabricating a moisture barrier having at least a polymer layer, and interfacial layer, and a barrier layer. The polymer layer may be fabricated from any suitable polymer including, but not limited to, fluoropolymers such as polyethylene terephthalate (PET) or polyethylene naphthalate (PEN), or ethylene-tetrafluoroethylene (ETFE). The interfacial layer may be formed by atomic layer deposition (ALD). In embodiments featuring an ALD interfacial layer, the deposited interfacial substance may be, but is not limited to, Al.sub.2O.sub.3, AlSiO.sub.x, TiO.sub.2, and an Al.sub.2O.sub.3/TiO.sub.2 laminate. The barrier layer associated with the interfacial layer may be deposited by plasma enhanced chemical vapor deposition (PECVD). The barrier layer may be a SiO.sub.xN.sub.y film.

  14. Barriers to screening mammography.

    PubMed

    Sarma, Elizabeth A

    2015-01-01

    Breast cancer (BRCA) is the second most commonly diagnosed cancer among women in the USA, and mammography is an effective means for the early detection of BRCA. Identifying the barriers to screening mammography can inform research, policy and practice aiming to increase mammography adherence. A literature review was conducted to determine common barriers to screening mammography adherence. PsycINFO and PubMed databases were searched to identify studies published between 2000 and 2012 that examined barriers associated with reduced mammography adherence. Three thematic groups of barriers, based on social ecology, were identified from the literature: healthcare system-level, social and individual-level barriers. Researchers must consider screening behaviour in context and, therefore, should simultaneously consider each level of barriers when attempting to understand screening behaviour and create interventions to increase mammography adherence.

  15. Barriers and Strategies in Guideline Implementation—A Scoping Review

    PubMed Central

    Fischer, Florian; Lange, Kerstin; Klose, Kristina; Greiner, Wolfgang; Kraemer, Alexander

    2016-01-01

    Research indicates that clinical guidelines are often not applied. The success of their implementation depends on the consideration of a variety of barriers and the use of adequate strategies to overcome them. Therefore, this scoping review aims to describe and categorize the most important barriers to guideline implementation. Furthermore, it provides an overview of different kinds of suitable strategies that are tailored to overcome these barriers. The search algorithm led to the identification of 1659 articles in PubMed. Overall, 69 articles were included in the data synthesis. The content of these articles was analysed by using a qualitative synthesis approach, to extract the most important information on barriers and strategies. The barriers to guideline implementation can be differentiated into personal factors, guideline-related factors, and external factors. The scoping review revealed the following aspects as central elements of successful strategies for guideline implementation: dissemination, education and training, social interaction, decision support systems and standing orders. Available evidence indicates that a structured implementation can improve adherence to guidelines. Therefore, the barriers to guideline implementation and adherence need to be analysed in advance so that strategies that are tailored to the specific setting and target groups can be developed. PMID:27417624

  16. Steric exclusion chromatography for purification of cell culture-derived influenza A virus using regenerated cellulose membranes and polyethylene glycol.

    PubMed

    Marichal-Gallardo, Pavel; Pieler, Michael M; Wolff, Michael W; Reichl, Udo

    2017-02-03

    Steric exclusion chromatography has been used for the purification of proteins and bacteriophages using monoliths. The operation is carried out by mixing a crude sample containing the target species with a predetermined concentration and molecular weight of polyethylene glycol (PEG) and loading it onto a non-reactive hydrophilic surface. Product capture occurs by the mutual steric exclusion of PEG between the product and the matrix. Selectivity is significantly influenced by target product size. Product elution is achieved by decreasing the PEG concentration. In this study, a 75cm(2) cellulose membrane adsorber was used for the purification of a clarified and inactivated influenza A virus broth produced in a 5L bioreactor using suspension Madin Darby canine kidney cells. Product recovery was above 95% based on hemagglutination activity and single radial immunodiffusion assays. Maximum depletion of double stranded host cell DNA and total protein was 99.7% and 92.4%, respectively. Purified virus particles showed no aggregation with a monodisperse peak around 84nm. 250mL of the clarified inactivated virus broth was purified within 40min. The surface area productivity based on the recovery of the viral hemagglutinin antigen was 28-50mgm(-2)h(-1) depending on the feed and loading conditions.

  17. Steric effect for proton, hydrogen-atom, and hydride transfer reactions with geometric isomers of NADH-model ruthenium complexes.

    PubMed

    Cohen, Brian W; Polyansky, Dmitry E; Achord, Patrick; Cabelli, Diane; Muckerman, James T; Tanaka, Koji; Thummel, Randolph P; Zong, Ruifa; Fujita, Etsuko

    2012-01-01

    Two isomers, [Ru(1)]2+ (Ru = Ru(bpy)2, bpy = 2,2'-bipyridine, 1 = 2-(pyrid-2'-yl)-1-azaacridine) and [Ru(2)]2+ (2 = 3-(pyrid-2'-yl)-4-azaacridine), are bioinspired model compounds containing the nicotinamide functionality and can serve as precursors for the photogeneration of C-H hydrides for studying reactions pertinent to the photochemical reduction of metal-C1 complexes and/or carbon dioxide. While it has been shown that the structural differences between the azaacridine ligands of [Ru(1)]2+ and [Ru(2)]2+ have a significant effect on the mechanism of formation of the hydride donors, [Ru(1HH)]2+ and [Ru(2HH)]2+, in aqueous solution, we describe the steric implications for proton, net-hydrogen-atom and net-hydride transfer reactions in this work. Protonation of [Ru(2*-)] in aprotic and even protic media is slow compared to that of [Ru(1*-)]+. The net hydrogen-atom transfer between *[Ru(1)]2+ and hydroquinone (H2Q) proceeds by one-step EPT, rather than stepwise electron-proton transfer. Such a reaction was not observed for *[Ru(2)]2+ because the non-coordinated N atom is not easily available for an interaction with H2Q. Finally, the rate of the net hydride ion transfer from [Ru(1HH)]2+ to [Ph3C]+ is significantly slower than that of [Ru (2HH)]2+ owing to steric congestion at the donor site.

  18. Steric interactions lead to collective tilting motion in the ribosome during mRNA–tRNA translocation

    PubMed Central

    Nguyen, Kien; Whitford, Paul C.

    2016-01-01

    Translocation of mRNA and tRNA through the ribosome is associated with large-scale rearrangements of the head domain in the 30S ribosomal subunit. To elucidate the relationship between 30S head dynamics and mRNA–tRNA displacement, we apply molecular dynamics simulations using an all-atom structure-based model. Here we provide a statistical analysis of 250 spontaneous transitions between the A/P–P/E and P/P–E/E ensembles. Consistent with structural studies, the ribosome samples a chimeric ap/P–pe/E intermediate, where the 30S head is rotated ∼18°. It then transiently populates a previously unreported intermediate ensemble, which is characterized by a ∼10° tilt of the head. To identify the origins of head tilting, we analyse 781 additional simulations in which specific steric features are perturbed. These calculations show that head tilting may be attributed to specific steric interactions between tRNA and the 30S subunit (PE loop and protein S13). Taken together, this study demonstrates how molecular structure can give rise to large-scale collective rearrangements. PMID:26838673

  19. Electronic and steric effects: how do they work in ionic liquids? The case of benzoic acid dissociation.

    PubMed

    D'Anna, Francesca; Marullo, Salvatore; Vitale, Paola; Noto, Renato

    2010-07-16

    The need to have a measure of the strength of some substituted benzoic acids in ionic liquid solution led us to use the protonation equilibrium of sodium p-nitrophenolate as a probe reaction, which was studied by means of spectrophotometric titration at 298 K. In order to evaluate the importance of electronic effect of the substituents present on the aromatic ring, both electron-withdrawing and -donor substituents were taken into account. Furthermore, to have a measure of the importance of the steric effect of the substituents both para- and ortho-substituted benzoic acids were analyzed. The probe reaction was studied in two ionic liquids differing for the ability of the cation to give hydrogen bond and pi-pi interactions, namely [bm(2)im][NTf(2)] and [bmpyrr][NTf(2)]. Data collected show that benzoic acids are less dissociated in ionic liquid than in water solution. Furthermore, the equilibrium constant values seem to be significantly affected by both the nature of ionic liquid cation and the structure of the acid. In particular, the ortho-steric effect seems to operate differently in water and in the aromatic ionic liquid, determining in this solvent medium a particular behavior for ortho-substituted benzoic acids.

  20. Reactivity versus steric effects in fluorinated ketones as esterase inhibitors: a quantum mechanical and molecular dynamics study

    PubMed Central

    Rayo, Josep; Muñoz, Lourdes; Rosell, Gloria; Hammock, Bruce D.; Guerrero, Angel

    2010-01-01

    Carboxylesterases (CEs) are a family of ubiquitous enzymes with broad substrate specificity, and their inhibition may have important implications in pharmaceutical and agrochemical fields. One of the most potent inhibitors both for mammalian and insect CEs are trifluoromethyl ketones (TFMKs), but the mechanism of action of these chemicals is not completely understood. This study examines the balance between reactivity versus steric effects in modulating the activity against human carboxylesterase 1. The intrinsic reactivity of the ketone moiety is determined from quantum mechanical computations, which combine gas phase B3LYP calculations with hydration free energies estimated with the IEF/MST model. In addition, docking and molecular dynamics simulations are used to explore the binding mode of the inhibitors along the deep gorge that delineates the binding site. The results point out that the activity largely depends on the nature of the fluorinated ketone, since the activity is modulated by the balance between the intrinsic electrophilicity of the carbonyl carbon atom and the ratio between keto and hydrate forms. However, the results also suggest that the correct alignment of the alkyl chain in the binding site can exert a large influence on the inhibitory activity, as this effect seems to override the intrinsic reactivity features of the fluorinated ketone. Overall, the results sustain a subtle balance between reactivity and steric effects in modulating the inhibitory activity of TFMK inhibitors. PMID:20676708